RESUMO
A pharmacokinetic study of anticancer drugs was carried out in 18 Hodgkin's lymphoma male patients. The anticancer drugs were administered to the patient by a standard procedure and a validated HPLC method was used for plasma concentration determination. Maximum plasma concentration [C[max]] of Adriamycin, Bleomycin, Vinblastine and Dacarbazine [ABVD] were 7.71, 4.32, 7.95 and 6.51 micro g/ml respectively. Adriamycin and Dacarbazine exhibited longer T[max] compared to Bleomycin and Vinblastine. Area under the curve values of ABVD were 118.30, 82.11, 245.54 and 86.62 micro g/ml h. The elimination rate constant of Dacarbazine was highest. Vinblastine exhibited highest half-life and mean residence time. Clearances of ABVD were 346.69, 2499.44, 45.90 and 5800.05ml/h. The apparent volume of distribution was highest for Dacarbazine and lowest for Vinblastine. The pharmacokinetic parameters can be utilized for monitoring of plasma concentrations, therapeutic drug monitoring and dosage adjustments to optimize anticancer efficacy in patients of Hodgkin's lymphoma
RESUMO
This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.