Biomaterial Database

Pharmacokinetic and tolerability profile of twice-daily saquinavir hard gelatin capsules and saquinavir soft gelatin capsules boosted with ritonavir in healthy volunteers. 2003

M Kurowski, and T Sternfeld, and A Sawyer, and A Hill, and C Möcklinghoff

HIV-Laboratory, c/o Auguste Viktoria Hospital, Berlin, Germany. labor-kurowski@t-online.de

OBJECTIVE To evaluate the pharmacokinetics and safety of a boosted saquinavir (SQV)/ritonavir (RTV) combination, administered as either the hard gelatin capsule (HGC) or soft gelatin capsule (SGC) formulation of SQV, in 24 healthy volunteers. METHODS This was a single-centre, open-label, randomized, 2 x 2 crossover study. Twelve subjects were randomized to receive SQV/RTV 1000 mg/100 mg twice daily (BID) orally for 10 days, as either the HGC or SGC formulation. The pharmacokinetic profile of SQV was determined on day 10. Subjects then crossed over to the opposite SQV formulation, and the pharmacokinetic profile was determined again on day 20. The primary analysis was the assessment of bioequivalence based on logarithmically transformed values for AUC(0-24 h) and Cmax for the two formulations. RESULTS There was a statistically significant increase in the geometric means of all the pharmacokinetic variables evaluated for SQV-HGC/RTV compared with SQV-SGC/RTV. A mean AUC0-24 h-value of 15.798 micro g/mL/h was reported for the HGC formulation compared with 11.655 micro g/mL/h for the SGC formulation (P = 0.0043). The SQV-HGC/RTV combination was better tolerated in terms of gastrointestinal system disorders. Furthermore, no elevations in triglycerides or total cholesterol were reported with SQV/RTV during the entire study period. CONCLUSIONS In healthy volunteers, RTV boosting of SQV-HGC produces plasma exposures at least comparable to SQV-SGC, which is accompanied by an improvement in gastrointestinal system disorders.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D002214	Capsules	Hard or soft soluble containers used for the oral administration of medicine.	Capsule,Microcapsule,Microcapsules
D002784	Cholesterol	The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.	Epicholesterol
D005780	Gelatin	A product formed from skin, white connective tissue, or bone COLLAGEN. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories.	Gelafusal
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D014280	Triglycerides	An ester formed from GLYCEROL and three fatty acid groups.	Triacylglycerol,Triacylglycerols,Triglyceride
D016015	Logistic Models	Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.	Logistic Regression,Logit Models,Models, Logistic,Logistic Model,Logistic Regressions,Logit Model,Model, Logistic,Model, Logit,Models, Logit,Regression, Logistic,Regressions, Logistic
D018592	Cross-Over Studies	Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)	Cross-Over Design,Cross-Over Trials,Crossover Design,Crossover Studies,Crossover Trials,Cross Over Design,Cross Over Studies,Cross Over Trials,Cross-Over Designs,Cross-Over Study,Crossover Designs,Crossover Study,Design, Cross-Over,Design, Crossover,Designs, Cross-Over,Designs, Crossover,Studies, Cross-Over,Studies, Crossover,Study, Cross-Over,Study, Crossover,Trial, Cross-Over,Trial, Crossover,Trials, Cross-Over,Trials, Crossover
D019258	Saquinavir	An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.	Invirase,Ro 31-8959,Saquinavir Mesylate,Saquinavir Monomethanesulfonate,Saquinivir,Monomethanesulfonate, Saquinavir,Ro 31 8959,Ro 318959