Pharmacokinetics of Azithromycin and the Combination of Ivermectin and Albendazole When Administered Alone and Concurrently in Healthy Volunteers

Abstract

Azithromycin is a critical component of an integrated disease elimination program against trachoma. This study was conducted to evaluate whether azithromycin has a pharmacokinetic interaction with the combination of ivermectin and albendazole. Eighteen healthy volunteers were administered single doses of azithromycin, ivermectin/albendazole, and the combination of the three agents in random, crossover fashion. To assess the presence of interactions, test (combination) and reference (single dose) data were compared using an estimation approach. Compared with reference phases, the geometric mean values for the combination arm's azithromycin AUC(0-t) and C(max) were increased approximately 13% and 20%, respectively, albendazole AUC(0-t) decreased by approximately 3% and C(max) increased approximately 3%, and ivermectin AUC(0-t) and C(max) were increased 31% and 27%, respectively. Albendazole sulfoxide AUC(0-t) and C(max) were decreased approximately 16% and 14%, respectively. All treatments were well tolerated. The interactions for azithromycin and albendazole were minimal although the increase in ivermectin exposure requires further study.

In Vitro and In Vivo Drug Interaction Study of Two Lead Combinations, Oxantel Pamoate plus Albendazole and Albendazole plus Mebendazole, for the Treatment of Soil-Transmitted Helminthiasis

“…However, before two drugs can be recommended for simultaneous treatment, in vitro and in vivo studies are necessary to rule out potential drug interactions. To our knowledge, to date only the coadministration of albendazole plus ivermectin has been thoroughly studied (8,9). The aim of the present work was therefore to assess the combined therapies of albendazole plus oxantel pamoate and albendazole plus mebendazole for potential drug-drug interactions.…”

“…When coadministering multiple drugs, drug-drug interactions should be ruled out. While the combination of albendazole plus ivermectin has been carefully evaluated in preclinical and clinical studies (8,9) albendazole combined with mebendazole or oxantel pamoate…”

Influence of Body Weight, Ethnicity, Oral Contraceptives, and Pregnancy on the Pharmacokinetics of Azithromycin in Women of Childbearing Age

“…Likely possibilities for the mechanism include an increase in the bioavailability or a reduction in the hepatobiliary excretion of azithromycin (3,4,34). The oral absorption and hepatobiliary elimination of azithromycin are mediated in part by the drug efflux transporters, multidrug resistance protein 2 (MRP2) and P-glycoprotein (3,5,8,21,52).…”

“…Likely possibilities for the mechanism include an increase in the bioavailability or a reduction in the hepatobiliary excretion of azithromycin (3,4,34). The oral absorption and hepatobiliary elimination of azithromycin are mediated in part by the drug efflux transporters, multidrug resistance protein 2 (MRP2) and P-glycoprotein (3,5,8,21,52). The decreased level of expression of MRP2 on the canalicular membrane of hepatocytes during pregnancy and following the administration of ethinyl estradiol in rats suggests a role for MRP2 in the hormone-mediated changes in the hepatobiliary clearance of azithromycin (11,12,32,53).…”

“…Standardized meals were provided at 4 and 10 h after the final dose. Approximately 5 ml of blood was collected through an indwelling catheter into a heparinized evacuated tube prior to and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3,4,6,8,12,24,48,72, and 96 h following the last azithromycin dose. Participants were discharged from the Clinical Research Center after the 12-h sample was taken and subsequently returned each morning for the next 4 days.…”