Clarithromycin Is Absorbed by an Intestinal Uptake Mechanism That Is Sensitive to Major Inhibition by Rifampicin: Results of a Short-Term Drug Interaction Study in Foals

Abstract

ABSTRACT:Pulmonary penetration of clarithromycin (CLR) in epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALCs) can be influenced by CYP3A4, by P-glycoprotein, and, according to our hypothesis, by a member of the organic anion-transporting protein (OATP) family, for which rifampicin (RIF) is inhibiting in single doses but inducing after long-term coadministration. To assess the partial inhibitory effect, we measured absorption and pulmonary distribution of CLR after short-term (2.5-day) coadministration of RIF, after which up-regulation is not expected. The drug interaction study was performed with five doses (12-h interval) of CLR (7.5 mg/kg) and RIF (10 mg/kg) in nine healthy foals; horse transporters are very similar in protein sequence and transcriptional regulation to the human analogs. RIF was equally distributed in ELF but reached half the plasma levels in BALCs. The deacetylated metabolite accumulated 1.4-to 6-fold in ELF and 8-to 60-fold in BALCs. CLR did not significantly influence the distribution of RIF. CLR and 14-hydroxyclarithromycin (14OH-CLR) accumulated approximately

Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals

“…However, a PK/PD index for the ELF in vivo has not yet been established. In addition, high AUC:MIC ratios are reached at the beginning of antimicrobial therapy with rifampicin before full emergence of PXR‐type enzyme induction and after combination with an enzyme‐inhibiting macrolide antibiotic, as shown in this group's former study in which clarithromycin was administered with 10 mg/kg bwt rifampicin twice per day (Table ) . To avoid any misunderstanding, the current work presents entirely descriptive pharmacokinetic parameters and AUC:MIC ratios for different treatment protocols with rifampicin that might be suitable to predict therapeutic efficacy in foals infected with R. equi .…”

In vivo disposition of doxorubicin is affected by mouse Oatp1a/1b and human OATP1A/1B transporters

“…HEK293 cells transduced with vector control, human (h)SLCO1A2, hSLCO1B1 and hSLCO1B3 cDNAs, a kind gift from Prof. Werner Siegmund and Dr. Markus Keiser, (University of Greifswald, Greifswald, Germany), were used to assess the uptake capacity for estradiol 17β‐ d ‐glucuronide and doxorubicin. The uptake transport study was carried out as described previously .…”

Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals

“…The clinical study was conducted in ten healthy warm‐blooded foals of the Oldenburger trait (six females, four males, age 42–56 days, body weight 105–148 kg). The animals included in the study were housed as described previously (Berlin et al., ; Peters et al., , ). Good health was confirmed by physical examination including sonography of the lung and routine clinical‐chemical and hematological screenings.…”