Dose-escalating study of the safety and pharmacokinetics of nelfinavir in HIV-exposed neonates

The pharmacokinetics of nelfinavir (NFV) in neonates younger than 4 weeks of age was assessed. Three cohorts of HIV-exposed neonates were enrolled in cohorts to receive 15, 30, and 45 mg of NFV/kg twice daily in combination with stavudine and didanosine for 4 weeks after birth. Trough NFV concentrations (C(min)) were measured at 1 and 7 days of age. Intensive pharmacokinetic evaluations were performed at 14 and 28 days of age. The median NFV C(min) values in the 15 mg/kg (6 patients), 30 mg/kg (5), and 45 mg/kg (11) cohorts at 1, 7, 14, and 28 days of age were 0.19, 1.21, 0.51, and 0.33; 1.02, 3.18, 0.73, and 0.55; and 0.67, 3.21, 0.70, and 0.73 mg/L, respectively. The median area under the plasma concentration-versus-time curve values over 12 hours in the three cohorts at 14 and 28 days of age were 14.4 and 8.7, 19.4 and 15.8, and 23.4 and 18.5 (h. mg)/L, respectively. No serious adverse events were observed. In conclusion, the systemic exposure of NFV decreased after 7 days of age, possibly because of hepatic enzyme maturation, autoinduction of NFV metabolism, and/or changes in NFV absorption. The highly variable systemic exposure observed in the study indicates that therapeutic drug monitoring seems warranted to ensure adequate NFV dosing in this populatio

Pharmacokinetics of Stavudine and Didanosine Coadministered with Nelfinavir in Human Immunodeficiency Virus-Exposed Neonates

We evaluated the pharmacokinetics of stavudine (d4T) and didanosine (ddI) in neonates. Eight neonates born to human immunodeficiency virus-infected mothers were enrolled to receive 1 mg of d4T per kg of body weight twice daily and 100 mg of ddI per m(2) once daily in combination with nelfinavir for 4 weeks after birth. Pharmacokinetic evaluations were performed at 14 and 28 days of age. For d4T, on days 14 and 28, the median areas under the concentration-time curves from 0 to 12 h (AUC(0–12)s) were 1,866 and 1,603, ng · h/ml, respectively, and the median peak concentrations (C(max)s) were 463 and 507 ng/ml, respectively. For ddI, on days 14 and 28, the median AUC(0–10)s were 1,573 and 1,562 h · ng/ml, respectively, and the median C(max)s were 627 and 687 ng/ml, respectively. Systemic levels of exposure to d4T were comparable to those seen in children, suggesting that the pediatric dose of 1 mg/kg twice daily is appropriate for neonates at 2 to 4 weeks of age. Levels of exposure to ddI were modestly higher than those seen in children. Whether this observation warrants a reduction of the ddI dose in neonates is unclear

Is Maternal Periodontal Disease a Risk Factor for Preterm Delivery?

Several studies have suggested an association between maternal periodontal disease and preterm delivery, but this has not been a consistent finding. In 2006–2007, the authors examined the relation between maternal periodontal disease and preterm delivery among 467 pregnant Thai women who delivered a preterm singleton infant (<37 weeks’ gestation) and 467 controls who delivered a singleton infant at term (≥37 weeks’ gestation). Periodontal examinations were performed within 48 hours after delivery. Participants’ periodontal health status was classified into 4 categories according to the extent and severity of periodontal disease. Logistic regression was used to estimate odds ratios and 95% confidence intervals. Preterm delivery cases and controls were similar with regard to mean probing depth, mean clinical attachment loss, and mean percentage of sites exhibiting bleeding on probing. After controlling for known confounders, the authors found that severe clinical periodontal disease was not associated with an increased risk of preterm delivery (odds ratio = 1.20, 95% confidence interval: 0.67, 2.16). In addition, there was no evidence of a linear increase in risk of preterm delivery or its subtypes associated with increasing severity of periodontal disease (Ptrend > 0.05). The results of this case-control study do not provide convincing evidence that periodontal disease is associated with preterm delivery or its subtypes among Thai women