Age-dependent Pharmacokinetics of Lamivudine in HIV-infected Children

Abstract

The recommended dose of lamivudine in children is higher when compared with adults: 4 mg/kg vs approximately 2 mg/kg (150 mg) and administered twice a day. Limited data are available to demonstrate that this increased dose results in adequate exposure to lamivudine in children with human immunodeficiency virus (HIV) infection. Data were selected from children who were using lamivudine for at least 2 weeks before a full pharmacokinetic (PK) study was conducted. Lamivudine PK parameters were significantly related to age. The age of 6 years appeared to be a cutoff for a change in PK parameters of lamivudine, with children <6 years of age (n=17) having a median area under the curve 43% lower and a median peak plasma concentration 47% lower (both P<0.001) than older children (n=34). In conclusion, further investigation of the relationship between decreased lamivudine exposure and treatment outcome and long-term resistance development in younger children with HIV infection is warranted.

Is the Recommended Once-Daily Dose of Lamivudine Optimal in West African HIV-Infected Children?

“…Thanks to the infants with a full pharmacokinetics profile, the two-compartment model parameters could be used, as previously described in children (17). The following observations support this model: (i) minimal and maximal concentrations and area under the curve were consistent with previous studies (4,5,14) (Table 3), and (ii) the apparent elimination clearance (CL/F ϭ 1.03 liters/h/kg) was consistent with previous studies (4,5). The population model was also used to investigate the effect of growth (body weight) and maturation (age) on pharmacokinetic parameters.…”

“…In children, maximal concentrations (C max ) and area under the concentration-time curve (AUC) from 0 to 24 h were not significantly lower with a once-daily administration of lamivudine than with a twice-daily administration (4). However, a few studies showed that younger children had a lower lamivudine exposure than older children and may be exposed to a subtherapeutic concentration, whether in a twice-daily or once-daily regimen (4,5,13,17). We may wonder whether this phenomenon is due to the effect of growth (body weight) and/or maturation (age) and which parameter should be taken into account to perform dose adjustment.…”

Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets

“…A previous study reported that the recommended daily lamivudine dosage (8 mg/kg) [6] leads to lower AUC 12h and C max in younger compared with older children [17]. Of note, however, is the fact that in our study younger children received relatively higher lamivudine doses per kilogram compared with older children, as a consequence of optimizing the dosing of three antiretroviral drugs across six weight bands, resulting in adequate plasma exposures across all ages.…”

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

“…Age-dependent pharmacokinetics has been reported for several drugs, including cisplatin, busulfan, thioguanine, etoposide, lamivudine, and mycophenolate mofetil [161][162][163][164][165][166]. Our studies showed that roscovitine elimination half-life was 14-fold higher in young rats compared to adults.…”