Lopinavir/ritonavir pharmacokinetics in a substitution of high-dose soft-gelatin capsule to tablet formulation.
Guidelines recommend that when soft-gelatin capsules of lopinavir/ritonavir are co-administered with CYP3A4-inducing agents, doses should be increased to 4 capsules (533 mg/133 mg) twice daily. No evidence is available to guide dosing of lopinavir/ritonavir in tablet formulation in this setting. A single-center study is conducted to compare the pharmacokinetics of high-dose lopinavir/ritonavir in 34 patients on stable HAART regimens including 4 soft-gelatin capsules twice daily who then switch to 3 tablets (600 mg/150 mg) twice daily. Median C(min) on soft-gelatin capsule and tablets is 4700 ng/mL (interquartile range [IQR] 2310, 6000 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively, for those on inducing agents (n = 17). For patients not on inducing agents (n = 17), median C(min) on soft-gelatin capsule and tablets is 5170 ng/mL (IQR 3640, 6210 ng/mL) and 5640 ng/mL (IQR 4290, 8080 ng/mL), respectively. Among treatment-experienced patients on lopinavir/ritonavir capsules 533/133 mg twice daily, a switch to tablets 600/150 mg twice daily produces comparable pharmacokinetics, regardless of whether they receive concomitant CYP3A4-inducing antiretroviral agents.
Hull
Mark W
MW
Canadian HIV Trials Network, Vancouver, Canada.
Harris
Marianne
M
Lima
Viviane
V
Guillemi
Silvia
S
Harrigan
P Richard
PR
Montaner
Julio S G
JS
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002214:Capsules; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005780:Gelatin / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets
D019380:Anti-HIV Agents; D002214:Capsules; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D013607:Tablets; D061466:Lopinavir; D005780:Gelatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019438:Ritonavir