Pharmacokinetics and Pulmonary Distribution of Clarithromycin and Rifampicin after Concomitant and Consecutive Administration in Foals.

The research article discusses a study on how the administration of two antibiotics, rifampicin (RIF) and clarithromycin (CLA), affects their absorption and distribution in the lungs in foals. The study aimed to determine the interaction between these drugs when administered all at once or consecutively, and how this interaction affects treatment of lung abscesses.

Research Methodology

• The study was conducted using 12 healthy foals. Each was given a dose of CLA (7.5 mg/kg) and RIF (10 mg/kg) either simultaneously or 4 hours apart.
• The researchers measured the affinity, or the strength of attraction, of CLA to several human and foal proteins using two different types of cells: Sf9-derived inside-out membrane vesicles and transfected HEK293.
• RIF’s ability to induce ABCB1, the gene associated with P-gp protein, and CLA’s affinity to the equine P-gp were studies using primary equine hepatocytes.

Key Findings

• When RIF was given alongside CLA, the bioavailability of CLA (the proportion which enters circulation and is able to have an effect) reduced significantly, from around 40% to less than 5%, and it reached its maximum concentration in the blood approximately 2-3 hours earlier.
• The loss of bioavailability was not connected with an increase in exposure to 14-hydroxyclarithromycin (14-OH-CLA), a metabolite of CLA.
• When RIF was administered 4 hours after CLA, the bioavailability and lung penetration of CLA approximately doubled as compared to simultaneous administration.
• In vitro tests showed that CLA has affinity to both human and foal P-gp proteins.
• Rifampicin induced the expression of the ABCB1 mRNA in 7 out of 8 duodenal biopsy specimens and in primary equine hepatocytes.

Conclusion

The primary finding is that the undesirable effect of RIF on the oral absorption and pulmonary distribution of CLA is linked to its ability to induce production of the intestinal P-gp protein. As a result, the researchers suggest administering the drugs consecutively, rather than at the same time, to avoid competition in their uptake by the intestines. Nonetheless, the researchers note that while this approach improves drug exposure significantly, it is still not sufficient to be clinically relevant.