title: Bioavailability of nevirapine in rats after oral and subcutaneous administration, in vivo absorption from gastrointestinal segments and effect of bile on its absorption from duodenum.
abstract: Nevirapine is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type-1. The usual dosing regimen is 200 mg twice/day. Reducing the dosing frequency would significantly improve treatment adherence and quality of life of patients. To study new forms of administration, it is necessary to do pre-clinical studies and know the absorption characteristics of nevirapine in laboratory animals. However, there are no studies about its bioavailability in rats and hardly any about its pharmacokinetic. The objectives of this study were to describe the pharmacokinetics of nevirapine in rats after intravenous, oral and subcutaneous administration, to assess its absorption by different regions of the gastrointestinal tract and to evaluate the effect of bile on its intestinal absorption. Nevirapine was well absorbed after oral and subcutaneous administration and the bioavailability estimated in rats (91% for both administration routes) was practically equal to that reported in humans (91-93%) after oral administration of therapeutic doses. Nevirapine was absorbed from the duodenum, ileum and colon, while absorption from the stomach was very low. The rate of absorption was in the order: duodenum>ileum>colon>stomach. The presence of bile in the duodenum increased the absorption rate of nevirapine.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Avda. V. Andrés Estellés, s/n, 46100-Burjassot, Valencia, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Usach
authors.forename: José-Esteban
authors.initials: JE
authors.lastname: Peris
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001682:Biological Availability; D004386:Duodenum / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007408:Intestinal Absorption; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013045:Species Specificity
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine