PK of once daily lopinavir/r in children
Polly Clayden, HIV i-Base
A report from Glenda Verweel et al from University Medical Centre in Rotterdam evaluated the pharmacokinetics of children on a QD dosing schedule of lopinavir/ritonavir.
A group of 14 children on stable antiretroviral therapy with HIV-1 RNA below 50 copies for at least six months were switched to receive LPV/r 460/115 mg/m2 QD with zidovudine and lamivudine BID as part of the RONDO trial. The LPV/r dose was given with food.
Samples were taken at 0, 2, 4, 6, 8, 12, 18 and 24 hours post dose. The target range for Cmin was 1.0mg/L. The children received a median dose of 400mg LPV (range 282-533mg). The median dose per m2 was 461 mg (448-883 mg). The investigators reported steady state AUC (0-24h), Cmax, Tmax and Cmin (24h) to be similar to LPV/r dosed at 800/200 mg QD in adults.
Of the children, only 3/14 had Cmin (24h) levels considered to be too low, leading to dose increase. At three months follow up, 12/13 children for whom data were available had HIV-1 RNA <50 copies/mL and one child had 52 copies/mL.
Like pregnant women, these last two studies show that if ever there is a population for which TDM is strongly indicated it is children.
Verweel G, van der Lee M, de Groot R et al. Pharmacokinetics of once daily lopinavir/ritonavir in HIV-infected children. Abstract 7.1