Assessment of nevirapine bioavailability from targeted sites in the human gastrointestinal tract.
This study investigated absorption of nevirapine (NVP) from targeted sites of the gastrointestinal tract using remotely activated capsules and gamma scintigraphy. A total of 24 participants were randomized to receive 50 mg NVP orally as a suspension or via remotely activated capsules for release into the ascending colon. The 24 participants were then rerandomized into parallel groups of n = 8 for drug release into the ileum, jejunum, or descending colon. The mean gastric emptying time of capsules ranged from 0.88 to 3.35 hours. The small intestinal and colon transit time ranged from 4.08 to 7.76 hours and 17.6 to 21.2 hours, respectively, and capsule recovery time ranged from 27.6 to 34.4 hours. The relative bioavailability ratio of NVP in the jejunum was 1.06 (90% confidence interval [CI]: 1.00-1.12) compared to suspension. In the ileum, ascending colon, and descending colon, bioavailability decreased to 0.89 (0.80-0.99), 0.82 (0.71-0.95), and 0.58 (0.22-1.53), respectively. The absorption rate decreased by approximately 10-fold from the jejunum (3.83 h(-1)) to the descending colon (0.338 h(-1)), and t(max) increased from 2.42 hours (jejunum) to 16.3 hours (descending colon). Overall, NVP is absorbed from all 4 sites of the gastrointestinal tract, and the rate of absorption decreased from the jejunum to the descending colon. Relative bioavailability of NVP was in the order of jejunum > ileum > ascending colon > descending colon.
Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Road, Ridgefield, CT 06877, USA. sreeraj.macha@boehringer-ingelheim.com
Sreeraj
S
Macha
Chan-Loi
CL
Yong
Thomas R
TR
MacGregor
Mark
M
Castles
Anne-Marie
AM
Quinson
Nicolas
N
Rouyrre
Ian
I
Wilding
D001682:Biological Availability; D002214:Capsules; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D013686:Telemetry
D002214:Capsules; D019829:Nevirapine