Metformin overdose can cause severe hypoglycemia in the absence of other antidiabetic drugs. Potential mechanisms of metformin-induced hypoglycemia include decreased hepatic glucose production, decreased glucose absorption, and poor oral intake.

The results for indinavir suggest that metabolic induction occurs during pregnancy, which apparently resolves spontaneously postpartum. This may warrant dosage adjustment during pregnancy. This induction is offset by concomitant use of ritonavir. Nelfinavir results were variable and, therefore, the impact of pregnancy on nelfinavir disposition was not fully determined.

ABSTRACT. Objective. Pharmacokinetic data obtained from children who have human immunodeficiency virus (HIV) infection are essential for the safe and effective use of antiretroviral agents in pediatric populations. The objective of this study was to assess the impact of body weight on the pharmacokinetic disposition of nelfinavir (NFV) in the absence and presence of nevirapine (NVP) and compare the pharmacokinetic profiles of twice-daily (BID) and three-times-daily (TID) NFV regimens.Methods. This was an intensive pharmacokinetic substudy nested in a phase II, multicenter, randomized, open-label trial. Forty-five HIV-infected children receiving NFV 30 mg/kg TID and 6 HIV-infected children receiving NFV 55 mg/kg BID were enrolled in this study and assigned to 1 of 4 stavudine-containing regimens, 3 containing NFV and 2 containing NVP. Area under the plasma concentration-time curves from 0 to 8 hours (AUC 0 -8 hours ) and from 0 to 12 hours (AUC 0 -12 hours ) for the TID and BID regimens, respectively, were determined. For comparative purposes, the AUC 0 -24 hours was also calculated for each regimen.Results. NFV exposure in the absence of NVP was decreased in children who were <25 kg compared with those who were >25 kg (a 2.6-fold difference in median AUC 0 -8 hours ). NFV pharmacokinetics in the presence of NVP did not differ between the <25 kg and >25 kg groups. The AUC 0 -24 hours for children who were <30 kg and on NFV BID was comparable to the AUC 0 -24 hours for children who were >25 kg and on NFV TID but was 2.7-fold greater than AUC 0 -24 hours for children who were <25 kg and on NFV TID.Conclusions. NFV in the absence of NVP resulted in less than half the drug exposure in children who were <25 kg compared with children who were >25 kg. NFV dosed at 55 mg/kg BID in children who are <30 kg provides comparable exposure to that measured in children who are >25 kg and receiving NFV 30 mg/kg TID. Pediatrics 2003;112:e220 -e227. URL: http://www. pediatrics.org/cgi/content/full/112/3/e220; pharmacokinetics, nelfinavir, children, HIV, protease inhibitor, nevirapine.

No abstract

No abstract