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A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the clinical evidence behind current renal impairment dosage recommendations for pediatric patients in a standard pediatric dosing handbook. The sources of recommendations and comparisons included the pediatric dosing handbook (Lexicomp), the U.S. Food and Drug Administration-approved manufacturer’s labels, and published studies in the literature. One hundred twenty-six drugs in Lexicomp had pediatric renal dosing recommendations. Only 14% (18 of 126) of Lexicomp pediatric renal dosing recommendations referenced a pediatric clinical study, and 15% of manufacturer’s labels (19 of 126) described specific dosing regimens for renally impaired pediatric patients. Forty-two products had published information on pediatric renal dosing, but 19 (45%) were case studies. When pediatric clinical studies were not referenced in Lexicomp, the renal dosing recommendations followed the adult and pediatric dosing recommendations on the manufacturer’s label. Clinical evidence in pediatric patients does not exist for most renal dosing recommendations in a widely used pediatric dosing handbook, and the adult renal dosing recommendations from the manufacturer’s label are currently the primary source of pediatric renal dosing information.

A lubricating microbicide gel designed for rectal and vaginal use would provide a behaviorally congruent strategy to enhance pre-exposure prophylaxis adherence and reduce HIV infection risk. In this study, we report the first-in-human evaluation of such a gel containing 1% IQP-0528, an investigational antiretroviral. Seven HIV-1-negative participants received one 10 mL rectal dose of radiolabeled 1% IQP-0528 gel. We assessed safety; IQP-0528 pharmacokinetics in plasma, and rectal and vaginal tissue; ex vivo local pharmacodynamics (PD); and colorectal distribution. The 1% gel was determined to be safe with one mild event attributed to study product and no effects on rectal tissue histology. All concentrations measured in plasma and vaginal tissue were below the limit of quantitation. Median IQP-0528 concentrations in rectal tissue exceeded the in vitro EC(95) against HIV-1 (0.07 ng/mg) by 3–5 h of dosing and remained above this concentration for at least 24 h, despite a 3-log reduction in concentration over this duration of time. Rectal tissue PD—assessed by ex vivo HIV challenge—demonstrated significant p24 antigen reduction 3–5 h postdose compared with baseline (p = .05), but not 24–26 h postdose (p = .75). Single-photon emission computed tomography/computed tomography imaging revealed that product distribution was localized to the rectosigmoid. The IQP-0528 gel possesses desirable features for a topical microbicide including: local safety with no systemic absorption, delivery of locally high IQP-0528 concentrations, and significant reductions in ex vivo HIV infectivity. However, the gel is limited by its rapid clearance and inability to penetrate vaginal tissues following rectal dosing. Clinical Trial Registration number: NCT03082690.