AUC O-infinity Research Articles

Pharmacokinetic investigation of nitrendipine encapsulated niosomal gel in rat plasma by RP-HPLC method

The investigation was intended to develop niosomal gel and determination of bioavailability of nitrendipine by pharmacokinetic method via using Albino Wistar rats. The drug nitrendipine carries the least bioavailability after oral administration of about 10–20% due to the first pass effect thus niosomes encapsulated with nitrendipine drug were prepared for transdermal application to avoid the problem associated with oral administration. Niosomes were prepared by method of film hydration using cholesterol and span 60 and further incorporated into gel base to prepare niosomal gel. A sensitive and suitable method for the investigation of nitrendipine in the plasma of rat was developed using RP-HPLC. The process involves nitrendipine extarction in dichloromethane/sodium hydroxide, using reversed phase HPLC using a Shimadzu, Japan (SPD-M20A), (C18, 250 × 4.6 mm, 5 µm particle size, Phenomenex) column and at 238 nm UV detection. The niosomes were found with 226 nm size and found homogenous after incorporating into the matrix of gel with optimum pH of 6.2. The various pharmacokinetic parameters Cmax (0.716 ± 0.058 µg/ml), Tmax (12 hrs), t1/2 (21.23 ± 0.65 hrs), AUC o-infinity (26.15 ± 3.76 µg/ml. hr), AUC o-t (19.593 ± 2.22 µg/ml. hr), mean residence time (MRT: 34.81 ± 1.58 hrs) confirmed improved bioavailability of nitrendipine drug after transdermal application compares to oral administration.

Pharmacokinetics of vincristine in cancer patients treated with nifedipine.

The pharmacokinetics of vincristine (VCR) after an intravenous bolus dose of 2 mg were studied in patients with cancer with and without a concomitant treatment with the calcium-entry blocker nifedipine (NIF). VCR concentrations were determined by a sensitive radioimmunoassay. Pharmacokinetic data were analyzed by a nonlinear weighted least-square regression program (SAS-NLIN). A tri-exponential model fitted the raw data better than a bi-exponential model in five of 14 (35%) patients treated with VCR alone and in seven of 12 (58%) patients treated with VCR plus NIF (P = NS). The T1/2 alpha was shorter in NIF-treated patients, whereas the T1/2 gamma was longer in the NIF-treated group. The NIF-treated group showed an increase in the AUC O-infinity and AUC 1 to 96 hours, and a decrease in the AUC 0 to 1 hour. Total plasma clearance of VCR and 7-day urinary excretion of VCR was reduced in the NIF-treated patients. These data suggest that, when VCR is administered to NIF-treated patients with cancer, there is a decrease in VCR clearance from the body. Theoretically, a greater cytotoxicity may be anticipated.