Pharmacokinetics of a once-daily regimen of lopinavir/ritonavir in HIV-1-infected children.
BACKGROUND
Lopinavir is an HIV protease inhibitor that is co-formulated with ritonavir. The approved paediatric dose is 230/57.5 mg/m2 twice daily. Once-daily dosing may offer an advantage to adherence. We studied the pharmacokinetics of lopinavir/ritonavir in a once-daily regimen in HIV-1-infected children.


METHODS
HIV-1-infected children on stable antiretroviral therapy with a viral load <50 copies/ml for at least 6 months received lopinavir/ritonavir 460/115mg/m2 once daily with zidovudine and lamivudine. Blood samples were collected at 0, 2, 4, 6, 8, 12, 18 and 24 h after observed intake during steady state. Target level for lopinavir Cmin was 1.0 mg/l, based on in vitro IC50 data.


RESULTS
Nineteen HIV-1-infected children with a median (range) age of 4.5 (1.4-12.9) years were enrolled. The median (interquartile range) dose of lopinavir was 456 (444-477) mg/m2. The mean (standard deviation) AUC0-24, Cmax and Cmin of lopinavir were 149.8 +/- 58.8 h*mg/l, 10.77 +/- 2.90 mg/l and 2.88 +/- 3.74 mg/l respectively. These values are comparable to data observed in adults using lopinavir/ritonavir 800/200 mg once daily. In 10/19 (53%) children Cmin was considered to be too low (<1.0 mg/l). Younger children more often experienced subtherapeutic trough levels.


CONCLUSIONS
Our findings indicate that 460/115 mg/m2 lopinavir/ritonavir once daily leads to mean pharmacokinetic parameters comparable to data of 800/200 mg lopinavir/ritonavir once daily in adults, although the variability observed in the trough levels is much higher in children. Further research, especially in young children, is necessary to determine whether a higher dosage of lopinavir/ritonavir once daily must be given to reach the target level for Cmin.
van der Lee
Manon
M
Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.vanderlee@akf.umcn.nl
Verweel
Gwenda
G
de Groot
Ronald
R
Burger
David
D
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir