The analyses indicate the existence of different response groups to treatment with Qutenza and an active control patch that may possibly be related to different pain mechanisms among these groups, despite a presumed common underlying disease process, and that require different treatment approaches among subgroups.

Sugammadex is a modified γ‐cyclodextrin which rapidly reverses rocuronium‐and vecuronium‐induced neuromuscular blockade. Previous studies suggest that sugammadex is mostly excreted unchanged via the kidneys. This single‐center, open‐label, non‐randomized study used 14C‐labeled sugammadex to further investigate the excretion, metabolic and pharmacokinetic (PK) profiles of sugammadex in six healthy male volunteers. 14C‐labeled sugammadex 4 mg/kg (0.025 MBq/kg of 14C‐radioactivity) was administered as a single intravenous bolus. Blood, urine, feces and exhaled air samples were collected at pre‐defined intervals for assessment of sugammadex by liquid chromatography‐mass spectrometry (LC‐MS) and for radioactivity measurements. Adverse events were also assessed. Excretion of sugammadex was rapid with ∼70% of the dose excreted within 6 h and ∼90% within 24 h. Less than 0.02% of radioactivity was excreted in feces or exhaled air. Ninety‐five percent of the radioactivity detected in urine could be attributed to sugammadex, as determined by LC‐MS, suggesting very limited metabolism of sugammadex. LC‐MS analysis of plasma samples found that sugammadex accounted for 100% of total 14C‐radioactivity in the plasma. In general, PK parameters determined from radioactivity and sugammadex plasma concentrations were very similar. Any adverse events were of mild‐to‐moderate intensity, and judged unrelated to sugammadex. These findings demonstrate that sugammadex is cleared rapidly, almost exclusively via the kidney, with minimal or no metabolism. Copyright © 2011 John Wiley & Sons, Ltd.

High doses of sugammadex (up to 96 mg/kg) were well tolerated in 12 of the 13 subjects. One male subject experienced several adverse events associated with a probable hypersensitivity reaction to sugammadex. Pharmacokinetics were dose linear over the range 32-96 mg/kg, with elimination predominantly via the renal route.

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L-praziquantel (PZQ) pharmacokinetic data were analyzed from two relative bioavailability Phase 1 studies in adult, healthy subjects with two new oral dispersion tablet (ODT) formulations of L-PZQ administered under various combinations of co-administration with food, water, and/or crushing. Linear mixed effects models adequately characterized the noncompartmental estimates of the pharmacokinetic profiles in both studies. Dose, food, and formulation were found to significantly affect L-PZQ exposure in both studies. The model for AUC was then extrapolated to children 2–5 years old accounting for enzyme maturation and weight. The predicted exposures were compared to an external Phase 1 study conducted by the Swiss Tropical and Public Health Institute using a currently marketed formulation (Cesol 600 mg immediate-release tablets) and found to be substantially lower than observed. A root cause analysis was completed to identify the reason for failure of the models. Various scenarios were proposed and tested. Two possible reasons for the failure were identified. One reason was that the model did not account for the reduced hepatic clearance seen in patients compared to the healthy volunteer population used to build the model. The second possible reason was that PZQ absorption appears sensitive to meal composition and the model did not account for differences in meals between a standardized Phase 1 unit and clinical sites in Africa. Further studies are needed to confirm our hypotheses.Electronic supplementary materialThe online version of this article (10.1007/s10928-018-9601-1) contains supplementary material, which is available to authorized users.