Dolutegravir is primarily metabolized via UGT1A1 with some contribution from CYP3A. After a single oral dose of [ 14 C] dolutegravir, 53% of the total oral dose was excreted unchanged in feces. Thirty-one percent of the total oral dose was excreted in urine, represented by an ether glucuronide of dolutegravir (% of total dose), a metabolite formed by oxidation at the benzylic carbon (% of total dose), and its hydrolytic N-dealkylation product (% of total dose). Renal elimination of unchanged drug was low (less than 1% of the dose).
Papular urticaria is characterized by chronic or recurrent eruptions of intensely pruritic papules, vesicles, and wheals caused by a hypersensitivity reaction to insect bites. 7 The lesions are usually grouped in linear clusters on exposed skin, but spare the genital, perianal, and axillary regions. Although the condition can occur in all age groups, it predominantly affects children. Intense pruritus and excoriations may be present. The rash of papular urticaria resolves much sooner than that of Gianotti-Crosti syndrome. Papular urticaria is diagnosed in patients of appropriate age with symmetrically distributed lesions, a history of hypersensitivity, and exposure to animals or insects. 7
Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to mg/kg. These doses are approximately and times, respectively, the human topical dose of clobetasol propionate cream and ointment. Abnormalities seen included cleft palate and skeletal abnormalities. In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately and times, respectively, the human topical dose of clobetasol propionate cream and ointment. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.