Pharmacokinetics of indinavir and ritonavir administered at 667 and 100 milligrams, respectively, every 12 hours compared with indinavir administered at 800 milligrams every 8 hours in human immunodeficiency virus-infected patients.

Human immunodeficiency virus (HIV) patients on nucleoside or nucleotide reverse transcriptase inhibitors with HIV RNA at <1,000 copies/ml were randomized in an open-label study to administration of combined indinavir/ritonavir (IDV/RTV) at 667/100 mg every 12 h (q12h) or IDV alone at 800 mg q8h to determine the regimens' pharmacokinetics. On day 14, plasma IDV and RTV levels were determined over 24 h. Noncompartmental pharmacokinetics (minimum concentration of drug in serum [C(min)], area under the concentration-time curve from 0 to 24 h [AUC(0-24)], and maximum concentration of drug in serum [C(max)]) were expressed as geometric mean values with 90% confidence intervals (CI). The primary hypothesis was that the lower bound of the protocol-specified 90% CI for the geometric mean C(min) ratio of the combination compared to IDV alone regimen would be >/=2. Twenty-seven patients were enrolled, and 24 (15 male; average age, 42 years) completed the study. The C(min), AUC(0-24), and C(max) for IDV/RTV compared to IDV alone were 1,511 versus 250 nM, 119,557 versus 77,034 nM . h, and 10,428 versus 10,407 nM, respectively. Corresponding relationships for IDV/RTV compared to IDV alone were a 6.0-fold increase in C(min) (90% CI, 4.0, 9.3), an increase in AUC(0-24) (1.5-fold, 90% CI, 1.2, 2.0), and no increase in C(max). Adverse events were similar and generally mild, with no cases of nephrolithiasis. The geometric mean ratio of IDV C(min) for IDV/RTV compared to IDV was at least 2 by a lower bound of the 90% CI, satisfying the primary hypothesis. The C(max) was not increased, suggesting an IDV/RTV 667/100-mg toxicity profile may be similar to that of unboosted IDV.

Application of Bayes theorem to aminoglycoside-associated nephrotoxicity: comparison of extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing.

The objective of this study was to examine the incidence of aminoglycoside-associated nephrotoxicity related to extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing by applying Bayes theorem. An electronic literature search of MEDLINE (1966-2003) and a manual search of references from published meta-analyses and review articles were performed. Studies using extended-interval dosing, individualized pharmacokinetic monitoring, or multiple-daily dosing and reported aminoglycoside-associated nephrotoxicity for patients > or = 16 years of age were included. Quality scores were assigned based on the rigor of definition of aminoglycoside-associated nephrotoxicity, duration of therapy, and length of follow-up of renal function after completion of therapy. Inclusion criteria were then based on these quality scores. Quantitative data on the incidence of aminoglycoside-associated nephrotoxicity were abstracted. Twelve extended-interval dosing studies (n = 916), 10 individualized pharmacokinetic monitoring studies (n = 2066), and 27 multiple-daily dosing studies (n = 4251) met the inclusion criteria. Prior probabilities of aminoglycoside-associated nephrotoxicity were derived from a combination of a review of published studies and expert judgment. The maximum densities for the final posterior probabilities of aminoglycoside-associated nephrotoxicity for extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing were located at 12% to 13%, 10% to 11%, and 13% to 14%, respectively. Application of Bayes theorem demonstrates that aminoglycoside dosing by individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity than extended-interval dosing or multiple-daily dosing.

Television viewing and television in bedroom associated with overweight risk among low-income preschool children.

CONTEXT: Television (TV) viewing is associated with obesity among school-aged children, adolescents, and adults, but this relationship has not been evaluated in preschool-aged children. OBJECTIVE: To describe the TV/video viewing habits of a multiethnic, low-income preschool population of children and to determine whether TV/video viewing is related to their adiposity. DESIGN: Cross-sectional survey of parents/guardians with measurements of children's height and weight. SETTING AND PARTICIPANTS: Two thousand seven hundred sixty-one adults with children, 1 through <5 years, from 49 New York State agencies of the Supplemental Nutrition Program for Women, Infants, and Children. OUTCOME MEASURES: Cross-sectional relationships between the amount of time the child spends viewing TV/video and the presence of a TV set in the child's bedroom, with the prevalence of overweight children (body mass index [BMI] >85th percentile) after adjustment for potential confounders. RESULTS: Mean TV/video viewing times were higher among black children and Hispanic children than white children and increased with the child's age. In multiple logistic regression, the odds ratio of children having a BMI >85th percentile was 1.06 (95% confidence interval [CI]: 1.004-1.11) for each additional hour per day of TV/video viewed, independent of child age, child sex, parental educational attainment, and race/ethnicity. Almost 40% of children had a TV set in their bedroom; they were more likely to be overweight and spent more time (4.6 hours per week) watching TV/video than children without a TV in their bedroom. In multiple logistic regression, the odds ratio of having a BMI >85th percentile was 1.31 (95% CI: 1.01-1.69) among those with a TV in their bedroom versus those without a TV, after statistical adjustment for child age, child sex, child TV/video viewing hours per week, maternal BMI, maternal education, and race/ethnicity. CONCLUSIONS: This study extends the association between TV viewing and risk of being overweight to younger, preschool-aged children. A TV in the child's bedroom is an even stronger marker of increased risk of being overweight. Because most children watch TV by age 2, educational efforts about limiting child TV/video viewing and keeping the TV out of the child's bedroom need to begin before then.