Nalbuphine is a semi-synthetic opioid indicated for the relief of moderate to severe pain. Its short half-life requires frequent injections in clinical practice, resulting in a greater incidence of adverse events. A prodrug of nalbuphine has been developed, dinalbuphine sebacate (DNS), dissolved in a simple oil-based injectable formulation, which could deliver and maintain an effective blood level of nalbuphine. An open-label, prospective, two-period study was performed in healthy volunteers to verify the extended blood concentration profile of nalbuphine. Twelve healthy Taiwanese were randomized to receive an intramuscular injection of 20 mg nalbuphine HCl and 150 mg DNS sequentially with a washout period of 5 days. To prevent DNS hydrolysis during sample analysis, the effect of four esterase inhibitors was evaluated in the quantitation of DNS in human whole blood and thenoyltrifluoroacetone was chosen. The bioavailability of nalbuphine from intramuscularly injected DNS relative to that from nalbuphine HCl was 85.4%. The mean absorption time of nalbuphine from DNS was 145.2 h. It took approximately 6 days for the complete release of DNS into the blood stream where DNS was rapidly hydrolysed to nalbuphine; suggesting a single injection of 150 mg DNS in our extended-release formulation could provide long-lasting pain relief.

Hair loss is a common adverse effect of antiepileptic drugs, especially in association with valproic acid and carbamazepine. The development of hair loss with newer antiepileptic drug therapy is relatively rare. We present a 15-year-old girl with frontal lobe epilepsy who developed hair loss after two months of topiramate adjunctive therapy. The hair loss was reversible upon discontinuation of topiramate, but recurred after reintroduction of the drug. Hair loss should be considered an adverse effect in topiramate adjunctive therapy. It may have significant cosmetic impact and psychosocial relevance, especially in children and young adults.