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Absence of circadian variation in the pharmacokinetics of lopinavir/ritonavir given as a once daily dosing regimen in HIV‐1‐infected patients
Author(s) -
Van Heeswijk R. P. G.,
Bourbeau M.,
Seguin I.,
Giguere P.,
Garber G. E.,
Cameron D. W.
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02337.x
Subject(s) - lopinavir/ritonavir , pharmacokinetics , ritonavir , lopinavir , interquartile range , dosing , medicine , cmin , pharmacology , geometric mean , morning , confidence interval , regimen , cmax , human immunodeficiency virus (hiv) , covid-19 , viral load , antiretroviral therapy , disease , family medicine , infectious disease (medical specialty) , statistics , mathematics
Aims To compare the pharmacokinetics of lopinavir/ritonavir (LPV/r) 800/200 mg administered once daily in the morning compared with the evening. Methods This was a randomized, two‐way, cross‐over study in HIV+ subjects. In each subject the pharmacokinetics of each drug were characterized after 2 weeks of LPV/r 800/200 mg administered once daily at 08.00 h and 19.00 h. On study days, LPV/r was taken with a standardized meal (800 kCal, 25% from fat) after fasting for at least 5 h. LPV/r concentrations were measured by LC‐MS/MS, and the data were analyzed by noncompartmental pharmacokinetic analysis. Results Fourteen subjects completed the study (all men, mean age/weight 44 year/81 kg). The median (interquartile range) LPV AUC(0,24 h), maximum plasma concentration ( C max ) and concentration at the end of the dosing interval ( C 24 h ) after am and pm dosing was, respectively, 143 (116–214) mg l −1 h, 12.8 (10.3–17.2) mg l −1 , 1.34 (0.58–3.25) mg l −1 , and 171 (120–232) mg l −1 h, 12.9 (8.22–16.3) mg l −1 , 1.15 (0.59–1.98) mg l −1 . The geometric mean ratio (GMR, am : pm) and 95% CI of the LPV AUC(0,24 h), C max , and C 24 h was 0.91 (0.79, 1.06), 1.11 (0.94, 1.32), and 1.19 (0.72, 1.96), respectively. The median ritonavir C max after am and pm dosing was 1.05 and 0.90 mg l −1 , respectively. The GMR (95% CI) of the RTV AUC(0,24 h), C max , and C 24 h was 0.93 (0.80, 1.08), 1.27 (1.00, 1.63), and 1.04 (0.68, 1.60), respectively. Administration of LPV/r in a once‐daily regimen was generally well tolerated. Conclusions No differences were observed in the pharmacokinetics of LPV/r after am or pm dosing with food, which suggests that this once daily combination, can be taken in the morning or evening. Such flexibility in dosing may improve adherence.