Effects of roxithromycin on the pharmacokinetics of loratadine after oral and intravenous administration of loratadine in rats.
The present study aimed to investigate the effect of roxithromycin on the oral and intravenous pharmacokinetics of loratadine in rats. The pharmacokinetic parameters ofloratadine were measured after an orally (4 mg/kg) and intravenously (1 mg/kg) administration of loratadine in the presence or absence of roxithromycin (2.0 or 5.0 mg/kg). Compared with the control (given loratadine alone), the area under the plasma concentration-time curve (AUC) was significantly (2.0 mg/kg, P < 0.05; 5.0 mg/kg, P < 0.01) increased by (76.8-119.2)% in the presence of roxithromycin after oral administration of loratadine. The peak plasma concentration (Cmax) was significantly (2.0 mg/kg, P < 0.05; 5.0 mg/kg, P < 0.01) increased by (45.1-97.6)% in the presence of roxithromycin after oral administration of loratadine. Consequently, the relative bioavailability (R.B.) of loratadine was increased by 1.77- to 2.19-fold. In contrast, roxithromycin had no effect on any pharmacokinetic parameters of loratadine given intravenously. It suggested that roxithromycin may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine most likely mediated by P-glycoprotein (P-gp) and/or cytochrome P450 (CYP) 3A4 in the intestine and/or liver. In conclusion, the presence of roxithromycin significantly enhanced the bioavailability of loratadine in rats, it may be due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of roxithromycin.
Li
Cheng
C
College of Pharmacy, Yanbian University, Jilin, 133000, China.
Kim
Cheul-Seol
CS
Yang
Jeong-Yeol
JY
Park
Yeong-Jin
YJ
Choi
Jun-Shik
JS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017336:Loratadine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015575:Roxithromycin / Q000008:administration & dosage / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D039563:Histamine H1 Antagonists, Non-Sedating; D015575:Roxithromycin; D017336:Loratadine; D003577:Cytochrome P-450 Enzyme System; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A