FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Pharm Sci / Few Drugs Display Flip-Flop Pharmacokinetics and These Are P...
Journal of pharmaceutical sciences2015; 104(9); 3229-3235; doi: 10.1002/jps.24505

Few Drugs Display Flip-Flop Pharmacokinetics and These Are Primarily Associated with Classes 3 and 4 of the BDDCS.

Abstract: This study was conducted to determine the number of drugs exhibiting flip-flop pharmacokinetics following oral (p.o.) dosing from immediate-release dosage forms and if they exhibit a common characteristic that may be predicted based on BDDCS classification. The literature was searched for drugs displaying flip-flop kinetics (i.e., absorption half-life larger than elimination half-life) in mammals in PubMed, via internet search engines and reviewing drug pharmacokinetic data. Twenty two drugs were identified as displaying flip-flop kinetics in humans (13 drugs), rat (nine drugs), monkey (three drugs), horse (two drugs), and/or rabbit (two drugs). Nineteen of the 22 drugs exhibiting flip-flop kinetics were BDDCS Classes 3 and 4. One of the three exceptions, meclofenamic acid (Class 2), was identified in the horse; however, it would not exhibit flip-flop kinetics in humans where the p.o. dosing terminal half-life is 1.4 h. The second, carvedilol, can be explained based on solubility issues, but the third sapropterin dihydrochloride (nominally Class 1) requires further consideration. The few drugs displaying p.o. flip-flop kinetics in humans are predominantly BDDCS Classes 3 and 4. New molecular entities predicted to be BDDCS Classes 3 and 4 could be liable to exhibit flip-flop kinetics when the elimination half life is short and should be suspected to be substrates for intestinal transporters.
© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
Get Full Text
Publication Date: 2015-05-25 PubMed ID: 26010239PubMed Central: PMC4536115DOI: 10.1002/jps.24505Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examined the occurrence of flip-flop pharmacokinetics in different types of drugs, and observed that this is largely associated with drugs belonging to the BDDCS Classes 3 and 4.

Study Purpose and Methods

  • The purpose of the study was to identify how many drugs show flip-flop pharmacokinetics following oral administration from immediate-release dosage forms, and to determine if there are any common characteristics that can be predicted based on their BDDCS classification.
  • The researchers carried out a comprehensive literature review searching for drugs showing flip-flop kinetics (where the absorption half-life is longer than the elimination half-life) in mammals. This was done by browsing through published articles in PubMed, utilizing internet search engines, and examining pharmacokinetic data of different drugs.

Findings

  • Twenty-two drugs were found to exhibit flip-flop pharmacokinetics in different types of mammals: 13 drugs in humans, 9 in rats, 3 in monkeys, 2 in horses, and 2 in rabbits.
  • The vast majority (19) out of these 22 drugs belong to the BDDCS Classes 3 and 4.
  • Regarding the remaining three drugs, one (meclofenamic acid, Class 2) was identified in horses, but it does not show flip-flop kinetics in humans; carvedilol’s behavior could be explained by solubility issues; and the behaviour of sapropterin dihydrochloride (Class 1) needs further study.

Implications

  • The research concludes that the small number of drugs displaying oral flip-flop pharmacokinetics in humans predominantly belong to the BDDCS Classes 3 and 4.
  • This suggests that new molecular entities predicted to fall under BDDCS Classes 3 and 4 could be prone to showing flip-flop kinetics, especially when the elimination half-life is short. Thus, they should be suspected to be substrates for intestinal transporters.

Cite This Article

APA
Garrison KL, Sahin S, Benet LZ. (2015). Few Drugs Display Flip-Flop Pharmacokinetics and These Are Primarily Associated with Classes 3 and 4 of the BDDCS. J Pharm Sci, 104(9), 3229-3235. https://doi.org/10.1002/jps.24505

Publication

Journal of pharmaceutical sciences
ISSN: 1520-6017
NlmUniqueID: 2985195R
Country: United States
Language: English
Volume: 104
Issue: 9
Pages: 3229-3235

Researcher Affiliations

Garrison, Kimberly L
  • Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California.
Sahin, Selma
  • Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California.
  • Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Benet, Leslie Z
  • Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California.

MeSH Terms

  • Administration, Oral
  • Animals
  • Biopharmaceutics / classification
  • Half-Life
  • Haplorhini
  • Horses
  • Humans
  • Intestinal Mucosa / metabolism
  • Kinetics
  • Membrane Transport Proteins / metabolism
  • Pharmaceutical Preparations / classification
  • Pharmaceutical Preparations / metabolism
  • Pharmacokinetics
  • Rabbits
  • Rats

Grant Funding

  • R21 GM075900 / NIGMS NIH HHS
  • GM61390 / NIGMS NIH HHS
  • U01 GM061390 / NIGMS NIH HHS
  • U19 GM061390 / NIGMS NIH HHS
  • GM75900 / NIGMS NIH HHS

References

This article includes 72 references
  1. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability.. Pharm Res 1995 Mar;12(3):413-20.
    pubmed: 7617530doi: 10.1023/a:1016212804288google scholar: lookup
  2. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system.. Pharm Res 2005 Jan;22(1):11-23.
    pubmed: 15771225doi: 10.1007/s11095-004-9004-4google scholar: lookup
  3. Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs.. Pharm Res 2009 Sep;26(9):2039-54.
    pmc: PMC2719753pubmed: 19568696doi: 10.1007/s11095-009-9924-0google scholar: lookup
  4. Yáñez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM. Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development.. Ther Deliv 2011 May;2(5):643-72.
    pmc: PMC3152312pubmed: 21837267doi: 10.4155/tde.11.19google scholar: lookup
  5. Han N, Yun HY, Kim IW, Oh YJ, Kim YS, Oh JM. Population pharmacogenetic pharmacokinetic modeling for flip-flop phenomenon of enteric-coated mycophenolate sodium in kidney transplant recipients.. Eur J Clin Pharmacol 2014 Oct;70(10):1211-9.
    pubmed: 25163792doi: 10.1007/s00228-014-1728-4google scholar: lookup
  6. Schumacher H, Smith RL, Williams RT. The metabolism of thalidomide: the spontaneous hydrolysis of thalidomide in solution.. Br J Pharmacol Chemother 1965 Oct;25(2):324-37.
    pmc: PMC1510736pubmed: 5866715doi: 10.1111/j.1476-5381.1965.tb02053.xgoogle scholar: lookup
  7. Philipson A, Stiernstedt G, Ehrnebo M. Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women.. Clin Pharmacokinet 1987 Feb;12(2):136-44.
    pubmed: 3829560doi: 10.2165/00003088-198712020-00004google scholar: lookup
  8. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans.. Drug Metab Dispos 2008 Feb;36(2):386-99.
    pubmed: 18006647doi: 10.1124/dmd.107.019083google scholar: lookup
  9. Trocóniz IF, Tillmann C, Liesenfeld KH, Schäfer HG, Stangier J. Population pharmacokinetic analysis of the new oral thrombin inhibitor dabigatran etexilate (BIBR 1048) in patients undergoing primary elective total hip replacement surgery.. J Clin Pharmacol 2007 Mar;47(3):371-82.
    pubmed: 17322149doi: 10.1177/0091270006297228google scholar: lookup
  10. Edick MJ, Gajjar A, Mahmoud HH, van de Poll ME, Harrison PL, Panetta JC, Rivera GK, Ribeiro RC, Sandlund JT, Boyett JM, Pui CH, Relling MV. Pharmacokinetics and pharmacodynamics of oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia.. J Clin Oncol 2003 Apr 1;21(7):1340-6.
    pubmed: 12663724doi: 10.1200/jco.2003.06.083google scholar: lookup
  11. He YL, Sadler BM, Sabo R, Balez S, Wang Y, Campestrini J, Laurent A, Ligueros-Saylan M, Howard D. The absolute oral bioavailability and population-based pharmacokinetic modelling of a novel dipeptidylpeptidase-IV inhibitor, vildagliptin, in healthy volunteers.. Clin Pharmacokinet 2007;46(9):787-802.
    pubmed: 17713976doi: 10.2165/00003088-200746090-00006google scholar: lookup
  12. He H, Tran P, Yin H, Smith H, Batard Y, Wang L, Einolf H, Gu H, Mangold JB, Fischer V, Howard D. Absorption, metabolism, and excretion of [14C]vildagliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans.. Drug Metab Dispos 2009 Mar;37(3):536-44.
    pubmed: 19074975doi: 10.1124/dmd.108.023010google scholar: lookup
  13. Hu P, Yin Q, Deckert F, Jiang J, Liu D, Kjems L, Dole WP, He YL. Pharmacokinetics and pharmacodynamics of vildagliptin in healthy Chinese volunteers.. J Clin Pharmacol 2009 Jan;49(1):39-49.
    pubmed: 18832295doi: 10.1177/0091270008325152google scholar: lookup
  14. He H, Tran P, Yin H, Smith H, Flood D, Kramp R, Filipeck R, Fischer V, Howard D. Disposition of vildagliptin, a novel dipeptidyl peptidase 4 inhibitor, in rats and dogs.. Drug Metab Dispos 2009 Mar;37(3):545-54.
    pubmed: 19074976doi: 10.1124/dmd.108.023002google scholar: lookup
  15. Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs.. AAPS J 2011 Dec;13(4):519-47.
    pmc: PMC3231854pubmed: 21818695doi: 10.1208/s12248-011-9290-9google scholar: lookup
  16. Melvin GC, Ellison SR, Monk CM, Bates TR. Existence of a flip-flop kinetic model for zidovudine (AZT) after oral administration.. Res Commun Chem Pathol Pharmacol 1990 Nov;70(2):193-204.
    pubmed: 2277865
  17. Mays DC, Dixon KF, Balboa A, Pawluk LJ, Bauer MR, Nawoot S, Gerber N. A nonprimate animal model applicable to zidovudine pharmacokinetics in humans: inhibition of glucuronidation and renal excretion of zidovudine by probenecid in rats.. J Pharmacol Exp Ther 1991 Dec;259(3):1261-70.
    pubmed: 1762074
  18. Patel BA, Chu CK, Boudinot FD. Pharmacokinetics and saturable renal tubular secretion of zidovudine in rats.. J Pharm Sci 1989 Jul;78(7):530-4.
    pubmed: 2778651doi: 10.1002/jps.2600780704google scholar: lookup
  19. Good SS, Durack DT, de Miranda P. Biotransformation in various species and in humans of 3′-azido-3′-deoxythymidine, a potential agent for the treatment of AIDS.. Fed Proc 1986;45.
  20. Qian MX, Finco TS, Mehta M, Viswanathan CT, Gallo JM. Pharmacokinetic evaluation of drug interactions with zidovudine. I: Probenecid and zidovudine in monkeys.. J Pharm Sci 1991 Nov;80(11):1007-11.
    pubmed: 1815049doi: 10.1002/jps.2600801102google scholar: lookup
  21. Blum MR, Liao SH, Good SS, de Miranda P. Pharmacokinetics and bioavailability of zidovudine in humans.. Am J Med 1988 Aug 29;85(2A):189-94.
    pubmed: 3165603
  22. Klecker RW Jr, Collins JM, Yarchoan R, Thomas R, Jenkins JF, Broder S, Myers CE. Plasma and cerebrospinal fluid pharmacokinetics of 3'-azido-3'-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases.. Clin Pharmacol Ther 1987 Apr;41(4):407-12.
    pubmed: 3549120doi: 10.1038/clpt.1987.49google scholar: lookup
  23. von Möllendorff E, Reiff K, Neugebauer G. Pharmacokinetics and bioavailability of carvedilol, a vasodilating beta-blocker.. Eur J Clin Pharmacol 1987;33(5):511-3.
    pubmed: 3428345doi: 10.1007/bf00544245google scholar: lookup
  24. Johansson IM, Kallings P, Hammarlund-Udenaes M. Studies of meclofenamic acid and two metabolites in horses--pharmacokinetics and effects on exercise tolerance.. J Vet Pharmacol Ther 1991 Sep;14(3):235-42.
    pubmed: 1744932doi: 10.1111/j.1365-2885.1991.tb00832.xgoogle scholar: lookup
  25. Snow DH, Baxter P, Whiting B. The pharmacokinetics of meclofenamic acid in the horse.. J Vet Pharmacol Ther 1981 Jun;4(2):147-56.
    pubmed: 7349327doi: 10.1111/j.1365-2885.1981.tb00724.xgoogle scholar: lookup
  26. Qi Y, Mould DR, Zhou H, Merilainen M, Musson DG. A prospective population pharmacokinetic analysis of sapropterin dihydrochloride in infants and young children with phenylketonuria.. Clin Pharmacokinet 2015 Feb;54(2):195-207.
    pmc: PMC4306193pubmed: 25338975doi: 10.1007/s40262-014-0196-4google scholar: lookup
  27. Estudante M, Morais JG, Soveral G, Benet LZ. Intestinal drug transporters: an overview.. Adv Drug Deliv Rev 2013 Oct;65(10):1340-56.
    pubmed: 23041352doi: 10.1016/j.addr.2012.09.042google scholar: lookup
  28. Morrissey KM, Wen CC, Johns SJ, Zhang L, Huang SM, Giacomini KM. The UCSF-FDA TransPortal: a public drug transporter database.. Clin Pharmacol Ther 2012 Nov;92(5):545-6.
    pmc: PMC3974775pubmed: 23085876doi: 10.1038/clpt.2012.44google scholar: lookup
  29. Food and Drug Administration. Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. www.fda.gov/cder/guidance/index.htm, part of U.S. Food and Drug Administration Center for Drug Evaluation and Research. http://www.fda.gov/Cder/
  30. Benet LZ, Larregieu CA. The FDA should eliminate the ambiguities in the current BCS biowaiver guidance and make public the drugs for which BCS biowaivers have been granted.. Clin Pharmacol Ther 2010 Sep;88(3):405-7.
    pmc: PMC4169211pubmed: 20668447doi: 10.1038/clpt.2010.149google scholar: lookup
  31. Chen ML, Yu L. The use of drug metabolism for prediction of intestinal permeability (dagger).. Mol Pharm 2009 Jan-Feb;6(1):74-81.
    pubmed: 19132929doi: 10.1021/mp8001864google scholar: lookup
  32. Hosey CM, Benet LZ. Predicting the extent of metabolism using in vitro permeability rate measurements and in silico permeability rate predictions.. Mol Pharm 2015 May 4;12(5):1456-66.
    pmc: PMC4666302pubmed: 25816851doi: 10.1021/mp500783ggoogle scholar: lookup
  33. Thöny B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions.. Biochem J 2000 Apr 1;347 Pt 1(Pt 1):1-16.
    pmc: PMC1220924pubmed: 10727395
  34. Cass LM, Efthymiopoulos C, Bye A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers.. Clin Pharmacokinet 1999;36 Suppl 1:1-11.
    pubmed: 10429835doi: 10.2165/00003088-199936001-00001google scholar: lookup
  35. Boulton DW, Fawcett JP. Enantioselective disposition of salbutamol in man following oral and intravenous administration.. Br J Clin Pharmacol 1996 Jan;41(1):35-40.
    pubmed: 8824691doi: 10.1111/j.1365-2125.1996.tb00156.xgoogle scholar: lookup
  36. Benmair Y, Fischel B, Frei EH, Gilat T. Evaluation of a magnetic method for the measurement of small intestinal transit time.. Am J Gastroenterol 1977 Nov;68(5):470-5.
    pubmed: 607797
  37. Shu Y, Brown C, Castro RA, Shi RJ, Lin ET, Owen RP, Sheardown SA, Yue L, Burchard EG, Brett CM, Giacomini KM. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics.. Clin Pharmacol Ther 2008 Feb;83(2):273-80.
    pmc: PMC2976713pubmed: 17609683doi: 10.1038/sj.clpt.6100275google scholar: lookup
  38. Saivin S, Hulot T, Chabac S, Potgieter A, Durbin P, Houin G. Clinical pharmacokinetics of acamprosate.. Clin Pharmacokinet 1998 Nov;35(5):331-45.
    pubmed: 9839087doi: 10.2165/00003088-199835050-00001google scholar: lookup
  39. Zornoza T, Cano-Cebrián MJ, Hipólito L, Granero L, Polache A. Evidence of a flip-flop phenomenon in acamprosate pharmacokinetics: an in vivo study in rats.. Biopharm Drug Dispos 2006 Oct;27(7):305-11.
    pubmed: 16799924doi: 10.1002/bdd.513google scholar: lookup
  40. Paintaud G, Alván G, Dahl ML, Grahnén A, Sjövall J, Svensson JO. Nonlinearity of amoxicillin absorption kinetics in human.. Eur J Clin Pharmacol 1992;43(3):283-8.
    pubmed: 1425893doi: 10.1007/bf02333024google scholar: lookup
  41. Tanigawara Y, Yamaoka K, Nakagawa T, Uno T. Moment analysis for the separation of mean in vivo disintegration, dissolution, absorption, and disposition time of ampicillin products.. J Pharm Sci 1982 Oct;71(10):1129-33.
    pubmed: 7143211doi: 10.1002/jps.2600711013google scholar: lookup
  42. Franke G, Schneider T, Siegmund W, Scherber A. Bioavailability studies of calcium dobesilate--a case of flip-flop kinetics.. Pharmazie 1985 Aug;40(8):562-3.
    pubmed: 4080804
  43. Walsh JS, Patanella JE, Unger SE, Brouwer KR, Miwa GT. The metabolism and excretion of carbovir, a carbocyclic nucleoside, in the rat.. Drug Metab Dispos 1990 Nov-Dec;18(6):1084-91.
    pubmed: 1981517
  44. Yeom YH, Remmel RP, Huang SH, Hua M, Vince R, Zimmerman CL. Pharmacokinetics and bioavailability of carbovir, a carbocyclic nucleoside active against human immunodeficiency virus, in rats.. Antimicrob Agents Chemother 1989 Feb;33(2):171-5.
    pmc: PMC171451pubmed: 2719460doi: 10.1128/aac.33.2.171google scholar: lookup
  45. Ruiz-Carretero P, Nacher A, Merino-Sanjuan M, Casabo VG. Pharmacokinetics and absolute bioavailability of oral cefuroxime axetil in the rat.. Int J Pharm 2000 Jul 20;202(1-2):89-96.
    pubmed: 10915930doi: 10.1016/s0378-5173(00)00420-8google scholar: lookup
  46. Padoin C, Tod M, Perret G, Petitjean O. Analysis of the pharmacokinetic interaction between cephalexin and quinapril by a nonlinear mixed-effect model.. Antimicrob Agents Chemother 1998 Jun;42(6):1463-9.
    pmc: PMC105623pubmed: 9624495doi: 10.1128/aac.42.6.1463google scholar: lookup
  47. Chen C. Some pharmacokinetic aspects of the lipophilic terfenadine and zwitterionic fexofenadine in humans.. Drugs R D 2007;8(5):301-14.
    pubmed: 17767395doi: 10.2165/00126839-200708050-00004google scholar: lookup
  48. Abd El-Aty AM, Goudah A, Abo El-Sooud K, El-Zorba HY, Shimoda M, Zhou HH. Pharmacokinetics and bioavailability of florfenicol following intravenous, intramuscular and oral administrations in rabbits.. Vet Res Commun 2004 Aug;28(6):515-24.
    pubmed: 15509025doi: 10.1023/b:verc.0000040241.06642.49google scholar: lookup
  49. Fredrick MJ, Pound DC, Hall SD, Brater DC. Furosemide absorption in patients with cirrhosis.. Clin Pharmacol Ther 1991 Mar;49(3):241-7.
    pubmed: 2007318doi: 10.1038/clpt.1991.23google scholar: lookup
  50. Lin CC, Luu T, Lourenco D, Yeh LT, Lau JY. Absorption, pharmacokinetics and excretion of levovirin in rats, dogs and cynomolgus monkeys.. J Antimicrob Chemother 2003 Jan;51(1):93-9.
    pubmed: 12493792doi: 10.1093/jac/dkg046google scholar: lookup
  51. Pentikäinen PJ, Neuvonen PJ, Penttilä A. Pharmacokinetics of metformin after intravenous and oral administration to man.. Eur J Clin Pharmacol 1979 Sep;16(3):195-202.
    pubmed: 499320doi: 10.1007/bf00562061google scholar: lookup
  52. Sambol NC, Chiang J, Lin ET, Goodman AM, Liu CY, Benet LZ, Cogan MG. Kidney function and age are both predictors of pharmacokinetics of metformin.. J Clin Pharmacol 1995 Nov;35(11):1094-102.
    pubmed: 8626883doi: 10.1002/j.1552-4604.1995.tb04033.xgoogle scholar: lookup
  53. Neale MG, Brown K, Foulds RA, Lal S, Morris DA, Thomas D. The pharmacokinetics of nedocromil sodium, a new drug for the treatment of reversible obstructive airways disease, in human volunteers and patients with reversible obstructive airways disease.. Br J Clin Pharmacol 1987 Oct;24(4):493-501.
    pmc: PMC1386312pubmed: 2825746doi: 10.1111/j.1365-2125.1987.tb03203.xgoogle scholar: lookup
  54. Nobutoshi W, Tomoo F, Kazumasa A, Nobuyoshi K. A flip-flop model for nitrofurantoin disposition in the rabbit following oral administration.. International Journal of Pharmaceutics 1984;21(1):85–98.
  55. Singhvi SM, Pan HY, Morrison RA, Willard DA. Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects.. Br J Clin Pharmacol 1990 Feb;29(2):239-43.
    pmc: PMC1380090pubmed: 2106337doi: 10.1111/j.1365-2125.1990.tb03626.xgoogle scholar: lookup
  56. Shin BS, Kim CH, Jun YS, Yoon CH, Rho JI, Lee KC, Han HS, Yoo SD. Oral absorption and pharmacokinetics of rebamipide and rebamipide lysinate in rats.. Drug Dev Ind Pharm 2004 Sep;30(8):869-76.
    pubmed: 15521332doi: 10.1081/ddc-200034577google scholar: lookup
  57. Bastain W, Boyce MJ, Stafford LE, Morton PB, Clarke DA, Marlow HF. Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers.. Eur J Clin Pharmacol 1988;34(5):469-73.
    pubmed: 2904884doi: 10.1007/bf01046704google scholar: lookup
  58. Luckner P, Brandsch M. Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1.. Eur J Pharm Biopharm 2005 Jan;59(1):17-24.
    pubmed: 15567297doi: 10.1016/j.ejpb.2004.07.008google scholar: lookup
  59. Uchida Y, Kamiie J, Ohtsuki S, Terasaki T. Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter.. Pharm Res 2007 Dec;24(12):2281-96.
    pubmed: 17939016doi: 10.1007/s11095-007-9453-7google scholar: lookup
  60. Mahony WB, Domin BA, Daluge SM, Zimmerman TP. Membrane permeation characteristics of abacavir in human erythrocytes and human T-lymphoblastoid CD4+ CEM cells: comparison with (-)-carbovir.. Biochem Pharmacol 2004 Nov 1;68(9):1797-805.
    pubmed: 15450945doi: 10.1016/j.bcp.2004.06.025google scholar: lookup
  61. Bakos E, Evers R, Sinkó E, Váradi A, Borst P, Sarkadi B. Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions.. Mol Pharmacol 2000 Apr;57(4):760-8.
    pubmed: 10727523doi: 10.1124/mol.57.4.760google scholar: lookup
  62. Hasegawa M, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y. Multidrug resistance-associated protein 4 is involved in the urinary excretion of hydrochlorothiazide and furosemide.. J Am Soc Nephrol 2007 Jan;18(1):37-45.
    pubmed: 17135398doi: 10.1681/asn.2005090966google scholar: lookup
  63. Zhou M, Xia L, Wang J. Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine.. Drug Metab Dispos 2007 Oct;35(10):1956-62.
    pmc: PMC2672958pubmed: 17600084doi: 10.1124/dmd.107.015495google scholar: lookup
  64. Tamai I, Takanaga H, Maeda H, Sai Y, Ogihara T, Higashida H, Tsuji A. Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids.. Biochem Biophys Res Commun 1995 Sep 14;214(2):482-9.
    pubmed: 7677755doi: 10.1006/bbrc.1995.2312google scholar: lookup
  65. Tokui T, Nakai D, Nakagomi R, Yawo H, Abe T, Sugiyama Y. Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2.. Pharm Res 1999 Jun;16(6):904-8.
    pubmed: 10397612doi: 10.1023/a:1018838405987google scholar: lookup
  66. Yamazaki M, Akiyama S, Ni'inuma K, Nishigaki R, Sugiyama Y. Biliary excretion of pravastatin in rats: contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter.. Drug Metab Dispos 1997 Oct;25(10):1123-9.
    pubmed: 9321514
  67. Abla N, Chinn LW, Nakamura T, Liu L, Huang CC, Johns SJ, Kawamoto M, Stryke D, Taylor TR, Ferrin TE, Giacomini KM, Kroetz DL. The human multidrug resistance protein 4 (MRP4, ABCC4): functional analysis of a highly polymorphic gene.. J Pharmacol Exp Ther 2008 Jun;325(3):859-68.
    pmc: PMC2612728pubmed: 18364470doi: 10.1124/jpet.108.136523google scholar: lookup
  68. Georges B, Galland S, Rigault C, Le Borgne F, Demarquoy J. Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine.. Biochem Pharmacol 2003 May 1;65(9):1483-8.
    pubmed: 12732360doi: 10.1016/s0006-2952(03)00110-2google scholar: lookup
  69. Jorajuria S, Dereuddre-Bosquet N, Becher F, Martin S, Porcheray F, Garrigues A, Mabondzo A, Benech H, Grassi J, Orlowski S, Dormont D, Clayette P. ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages.. Antivir Ther 2004 Aug;9(4):519-28.
    pubmed: 15456083
  70. Pan G, Giri N, Elmquist WF. Abcg2/Bcrp1 mediates the polarized transport of antiretroviral nucleosides abacavir and zidovudine.. Drug Metab Dispos 2007 Jul;35(7):1165-73.
    pubmed: 17437964doi: 10.1124/dmd.106.014274google scholar: lookup
  71. Ritzel MW, Yao SY, Huang MY, Elliott JF, Cass CE, Young JD. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1).. Am J Physiol 1997 Feb;272(2 Pt 1):C707-14.
    pubmed: 9124315doi: 10.1152/ajpcell.1997.272.2.c707google scholar: lookup
  72. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD. Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes.. Mol Membr Biol 2001 Apr-Jun;18(2):161-7.
    pubmed: 11463208doi: 10.1080/09687680110048318google scholar: lookup

Citations

This article has been cited 16 times.
  1. Eke AC, Gebreyohannes RD, Fernandes MFS, Pillai VC. Physiologic Changes During Pregnancy and Impact on Small-Molecule Drugs, Biologic (Monoclonal Antibody) Disposition, and Response. J Clin Pharmacol 2023 Jun;63 Suppl 1(Suppl 1):S34-S50.
    doi: 10.1002/jcph.2227pubmed: 37317492google scholar: lookup
  2. Liu Y, Cheng J, Liang L, Qian W, Ou M, Zhang M, Wang Y, Wang Y, Peng K, Jia J. A single-dose, randomized crossover study in healthy Chinese subjects to evaluate pharmacokinetics and bioequivalence of two capsules of calcium dobesilate 0.5 g under fasting and fed conditions. PLoS One 2023;18(4):e0284576.
    doi: 10.1371/journal.pone.0284576pubmed: 37083730google scholar: lookup
  3. Kiesel BF, Deppas JJ, Guo J, Parise RA, Clump DA, Bakkenist CJ, Beumer JH. Dose-dependent bioavailability, absorption-rate limited elimination, and tissue distribution of the ATR inhibitor BAY-1895344 (elimusertib) in mice. Cancer Chemother Pharmacol 2022 Jun;89(6):795-807.
    doi: 10.1007/s00280-022-04436-0pubmed: 35507041google scholar: lookup
  4. Zake DM, Kurlovics J, Zaharenko L, Komasilovs V, Klovins J, Stalidzans E. Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues. PLoS One 2021;16(4):e0249594.
    doi: 10.1371/journal.pone.0249594pubmed: 33826656google scholar: lookup
  5. Islam MK, Strand M, Saleeb M, Svensson R, Baranczewski P, Artursson P, Wadell G, Ahlm C, Elofsson M, Evander M. Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound. Sci Rep 2018 Jan 31;8(1):1925.
    doi: 10.1038/s41598-018-20362-9pubmed: 29386590google scholar: lookup
  6. Wenzler E, Ellis-Grosse EJ, Rodvold KA. Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers. Antimicrob Agents Chemother 2017 Sep;61(9).
    doi: 10.1128/AAC.00775-17pubmed: 28630194google scholar: lookup
  7. Benet LZ, Hosey CM, Ursu O, Oprea TI. BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev 2016 Jun 1;101:89-98.
    doi: 10.1016/j.addr.2016.05.007pubmed: 27182629google scholar: lookup
  8. Hosey CM, Chan R, Benet LZ. BDDCS Predictions, Self-Correcting Aspects of BDDCS Assignments, BDDCS Assignment Corrections, and Classification for more than 175 Additional Drugs. AAPS J 2016 Jan;18(1):251-60.
    doi: 10.1208/s12248-015-9845-2pubmed: 26589308google scholar: lookup
  9. Benet LZ, Sodhi JK. Mathematical Modeling in Drug Metabolism and Pharmacokinetics: Correct In Vitro, Not Always Valid In Vivo. Pharmaceuticals (Basel) 2026 Jan 15;19(1).
    doi: 10.3390/ph19010160pubmed: 41599757google scholar: lookup
  10. Daniels MH, Castro J, Lee YT, Gotur D, Knockenhauer KE, Grigoriu S, Lockbaum GJ, Cheong JE, Lu C, Brennan D, Buker SM, Liu J, Yao S, Sparling BA, Sickmier EA, Ribich S, Blakemore SJ, Silver SJ, Boriack-Sjodin PA, Duncan KW, Copeland RA. Discovery of ATX968: An Orally Available Allosteric Inhibitor of DHX9. J Med Chem 2025 May 8;68(9):9537-9554.
    doi: 10.1021/acs.jmedchem.5c00252pubmed: 40298172google scholar: lookup
  11. Chen S, Liu Y, Wang Y, Wen Z, Meng J, Yang Y, Zhang Y, Kong M, Chen G, Cao X. Determination of QLNC-3A6 in canine plasma by UHPLC-MS/MS and its application in pharmacokinetic studies. Vet Q 2024 Dec;44(1):1-11.
    doi: 10.1080/01652176.2024.2407174pubmed: 39625835google scholar: lookup
  12. Benet LZ, Sodhi JK. Commentary: Pharmacokinetic Theory Must Consider Published Experimental Data. Drug Metab Dispos 2024 Aug 14;52(9):932-938.
    doi: 10.1124/dmd.124.001735pubmed: 38942444google scholar: lookup
  13. Cracchiolo MJ, Davis L, Matiatos AP, Davini DW, Husnain M, Simpson RJ, Voudouris V, Katsanis E. Comparable efficacy of oral bendamustine versus intravenous administration in treating hematologic malignancies. Cancer Chemother Pharmacol 2024 Sep;94(3):361-372.
    doi: 10.1007/s00280-024-04688-ypubmed: 38878208google scholar: lookup
  14. Ramadan AEH, Elsayed MMA, Elsayed A, Fouad MA, Mohamed MS, Lee S, Mahmoud RA, Sabry SA, Ghoneim MM, Hassan AHE, Abd Elkarim RA, Belal A, El-Shenawy AA. Development and optimization of vildagliptin solid lipid nanoparticles loaded ocuserts for controlled ocular delivery: A promising approach towards treating diabetic retinopathy. Int J Pharm X 2024 Jun;7:100232.
    doi: 10.1016/j.ijpx.2024.100232pubmed: 38357578google scholar: lookup
  15. Wakuda H, Xiang Y, Sodhi JK, Uemura N, Benet LZ. An Explanation of Why Dose-Corrected Area Under the Curve for Alternate Administration Routes Can Be Greater than for Intravenous Dosing. AAPS J 2024 Jan 30;26(1):22.
    doi: 10.1208/s12248-024-00887-wpubmed: 38291293google scholar: lookup
  16. Kanan M, Atif S, Mohammed F, Balahmar Y, Adawi Y, AlSaleem R, Farhan A, Alghoribi M, Mohammed S, Alshanbari R, Fahad M, Kallab R, Mohammed R, Alassaf D, Hazza A. A Systematic Review on the Clinical Pharmacokinetics of Cephalexin in Healthy and Diseased Populations. Antibiotics (Basel) 2023 Sep 3;12(9).
    doi: 10.3390/antibiotics12091402pubmed: 37760698google scholar: lookup
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.