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Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations.

Abstract: Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 hours. Serum, urine, and endometrial GT concentrations were determined by a radioimmunoassay technique (sensitivity of 0.3 micrograms/ml of serum). Serum GT concentration data obtained from the terminal phase were best fitted by a 1-compartment open model with a biological half-life of 2.13 +/- 0.43 hours. Total body clearance and renal clearance were 1.69 +/- 0.41 and 1.40 +/- 0.26 ml/min/kg, respectively. Mean endometrial concentrations on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms/g. To achieve mean serum GT concentrations (micrograms/ml) at steady state of 6.47 +/- 1.51, a maximum steady-state concentration of 12.74 +/- 1.60, and a minimum steady-state concentration of 1.43 +/- 0.57, a dosage of 5 mg/kg every 8 hours is recommended. Serum urea nitrogen, serum creatinine, and the fractional clearance of sodium sulfanilate were determined before and after GT treatment. Renal function remained within the base-line range during 7 days of GT administration.
Publication Date: 1985-06-01 PubMed ID: 4026004
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research involves understanding how the drug Gentamicin behaves in the body of ponies, in terms of its absorption, distribution, metabolism, and elimination. The study found that to maintain certain levels of Gentamicin in the system, a dosage of 5 mg of the drug for each kg of body weight is recommended every 8 hours.

Study Design

  • The research was conducted on 6 healthy mares (female ponies). Each was given a dosage of Gentamicin of 5 mg per kg of their body weight, administered every 8 hours for a week, for a total of 21 doses.
  • Venous blood samples were taken from the mares before and one hour after the 5th, 10th, 14th, and 19th doses. This aimed to monitor the levels of the drug in the blood at different stages of treatment – before the dose (trough) and after the dose (peak).
  • Endometrial biopsies were also conducted on the fourth and seventh days. Urine was collected 24 hours after catheterization on Day 7. Serum, urine, and endometrial Gentamicin concentrations were measured using a radioimmunoassay technique.

Results

  • It was found that the data obtained from the terminal phase were best fitted by a one-compartment open model with a half-life of 2.13 +/- 0.43 hours. This shows how quickly the drug is metabolized and eliminates from the body.
  • The total body clearance and renal clearance rates were calculated to be 1.69 +/- 0.41 ml/min/kg and 1.40 +/- 0.26 ml/min/kg respectively. This means that the body and the kidneys eliminated the drug at these respective rates.
  • Endometrial concentrations observed on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms per gram respectively, showing an accumulation of the drug over the course of treatment.
  • It was calculated that a steady dosage of 5 mg per kg every 8 hours should achieve average serum Gentamicin concentrations at steady state of 6.47 +/- 1.51, a maximum concentration of 12.74 +/- 1.60, and a minimum concentration of 1.43 +/- 0.57. These results help in understanding the dosing practices required to maintain therapeutic drug levels.
  • While it was observed that renal function remained within the base-line range during 7 days of Gentamicin administration, serum urea nitrogen, serum creatinine, and fractional clearance of sodium sulfanilate were measured before and after Gentamicin treatment to monitor the drug’s possible effects on renal function.

Cite This Article

APA
Haddad NS, Pedersoli WM, Ravis WR, Fazeli MH, Carson RL. (1985). Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations. Am J Vet Res, 46(6), 1268-1271.

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 46
Issue: 6
Pages: 1268-1271

Researcher Affiliations

Haddad, N S
    Pedersoli, W M
      Ravis, W R
        Fazeli, M H
          Carson, R L

            MeSH Terms

            • Animals
            • Endometrium / metabolism
            • Female
            • Gentamicins / administration & dosage
            • Gentamicins / blood
            • Gentamicins / metabolism
            • Gentamicins / urine
            • Horses / metabolism
            • Injections, Intramuscular / veterinary
            • Kinetics
            • Models, Biological

            Citations

            This article has been cited 3 times.
            1. El-Hewaity M, Abd El Latif A, Soliman A, Aboubakr M. Comparative Pharmacokinetics of Cefquinome (Cobactan 2.5%) following Repeated Intramuscular Administrations in Sheep and Goats.. J Vet Med 2014;2014:949642.
              doi: 10.1155/2014/949642pubmed: 26464946google scholar: lookup
            2. El-Hewaity M. Influence of flunixin on the disposition kinetic of cefepime in goats.. Adv Pharmacol Sci 2014;2014:471517.
              doi: 10.1155/2014/471517pubmed: 24883058google scholar: lookup
            3. Brown SA, Sugimoto K, Smith GG, Garry FB. Improved sodium hydroxide digestion method without homogenization for extraction of gentamicin from renal tissue.. Antimicrob Agents Chemother 1988 Apr;32(4):595-7.
              doi: 10.1128/AAC.32.4.595pubmed: 3377470google scholar: lookup