JAC Advance Access originally published online on April 10, 2006
Journal of Antimicrobial Chemotherapy 2006 57(6):1168-1171; doi:10.1093/jac/dkl136
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Lopinavir/ritonavir exposure in treatment-naive HIV-infected children following twice or once daily administration
1 Department of Infectious Diseases, San Martino Hospital and University of Genoa Genoa, Italy 2 Bambin Gesù Children's Hospital Rome, Italy 3 Department of Pediatrics, L. Sacco Hospital Milan, Italy 4 Department of Pediatrics, University of Padua Padua, Italy
Received 12 January 2006; returned 7 February 2006; revised 13 March 2006; accepted 20 March 2006
*Correspondence address. Clinica Malattie Infettive, A.O.U. San Martino, Padiglione Patologie Complesse, Largo Rosanna Benzi 10, 16132 Genoa, Italy. Tel: +39-010-555-5142; Fax: +39-010-555-5132; E-mail: antonio.dibiagio{at}hsanmartino.liguria.it
Objectives: Lopinavir/ritonavir is approved for treatment of HIV-infected children at a dosage regimen of 230/57.5 mg/m2 twice daily. However, once daily administration could increase convenience and patient adherence. Our study aimed at evaluating whether inhibitory concentrations are maintained in plasma following administration of lopinavir/ritonavir once daily.
Patients and methods: Lopinavir/ritonavir was administered at the standard twice daily regimen to 21 HIV-infected children, as a component of their antiretroviral treatment. Following at least 1 month of administration, seven patients received a dose of 460/115 mg/m2 once daily for three consecutive days. After the third dose of once daily administration, blood samples were drawn at the following times: 0 (pre-dose), 1, 2 and 4 h following administration. The pre-dose (Cmin) and the peak (Cmax) concentrations were compared with the values obtained following twice daily administration in all the study patients.
Results: Median (interquartile range) Cmin with the once daily regimen was 1.59 (0.77–6.85) mg/L versus 7.90 (5.45–9.77) mg/L with the twice daily regimen (P < 0.05). Cmin was considered inhibitory for wild-type virus (>1.0 mg/L) in four out of seven patients. Cmax did not differ significantly between the once daily and twice daily regimens.
Conclusions: Our small pilot study suggests that lopinavir/ritonavir once daily may be a suitable regimen for antiretroviral-naive children. However, due to the high interindividual variability and low concentrations in some patients, therapeutic drug monitoring may be necessary to ensure that concentrations are adequate to inhibit viral replication. A formal clinical study of lopinavir/ritonavir once daily in treatment-naive children is warranted.
Keywords: pharmacokinetics , protease inhibitors , therapeutic drug monitoring
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