Pharmacokinetics And Bioequivalence Study Of Hydrocodone Bitartrate And Acetaminophen Tablets In Healthy Volunteers

Objective: To estabilish accurate and sensitive HPLC-UV and HPLC-MS methods for the determination of Acetaminophen and Hydrocodone in human plasma; To calculate the pharmacokinetics of Hydrocodone Bitartrate and Acetaminophen Tablets in Chinese healthy volunteers. To evaluate the bioequivalence of Hydrocodone Bitartrate and Acetaminophen test and reference in a randomized cross-over and two period design test.Methods: Twenty Chinese healthy volunteers were classified two groups randomized. A liquor of blood were taken from ulnar vein before and 0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0 hours after orally taken Hydrocodone Bitartrate and Acetaminophen Tablets test or reference, and immediately transferred to calparine tube and centrifuged, plasma was collected and stored at -20℃for analysis. HPLC-UV and HPLC-mass-spectrum methods were used to determine the plasma concentrations of Acetaminophen and Hydrocodone. The pharmacokinetic parameters of Hydrocodone and Acetaminophen were calculated with DAS and ANOVA, analysis of T-test confidence interval were conducted to evaluate the bioequivalence ofHydrocodone Bitartrate and Acetaminophen test and reference.Results: The main pharmacokinetics parameters of Acetaminophen in Hydrocodone Bitartrate and Acetaminophen test and reference were as following: t_1/2 was (3.900±1.926)h and (3.088±1.731)h, Tmax was (0.775±0.197)h and (0.763±0.190)h, Cmax was (15.932±3.695)μg·ml^-1 and (16.952±3.939)μg·ml^-1, AUC_0-24 was (64.270±26.625)μg·ml^-1·h and (64.723±26.297)μg·ml^-1·h, AUC_0-∞ was (67.716±33.219 )μg·ml^-1·h and (67.661±33.150)μg·ml^-1·h.The relative bioavailability of Acetaminophen of Hydrocodone Bitartrate and Acetaminophen test was 100.914%±14.508%.The main pharmacokinetics parameters of Hydrocodone in Hydrocodone Bitartrate and test and reference were as following: tl/2 was (5.377±0.862)h and (5.318±1.382)h, Tmax was (1.438±0.590)h and (1.513±0.604)h, Cmax was (21.722±6.102)ng/ml and (20.572±5.380)ng·ml-1, AUC0-24 was (135.493±33.835) ng·ml^-1·h and (133.009±30.810)ng·ml^-1·h, AUC_0-∞ was(142.386±35.767)ng·ml^-1·h and 139.243±31.540)ng·ml^-1·h.The relative bioavailability of Hydrocodone of Hydrocodone Bitartrate and Acetaminophen test was 102.9%±16.9%.Conclusions: 1. The assay was proved to be sensitive,accurate and convenient, and it is suitable for Hydrocodone and Acetaminophen pharmacokinetics studies after single oral doses of Hydrocodone Bitartrate and Acetaminophen Tablets. 2. The relative bioavailabilities of Acetaminophen and Hydrocodone in Hydrocodone Bitartrate and Acetaminophen Tablets were 100.914%±14.508% and 102.9%±16.9% respectively. 3. ANOVA analysis showed that no significant difference existed between the main pharmacokinetics parameters as AUC, Cmax and Tmax of Hydrocodone Bitartrate and Acetaminophen test and reference, as well as the periods, but in dividual statistical differences of existed. Further of t-test analysis showed that the hypothesis of bioequivalence were consistent with the fact among individuals, periods and preparations. Hydrocodone Bitartrate and Acetaminophen test and reference were bioequivalence.