OBJECTIVE Potency equivalents for anti-psychotic drugs are required to guide clinical dosing and for designing and interpreting research studies. Available dosing guidelines are limited by the methods and data from which they were generated. METHOD With a two-step Delphi method, the authors surveyed a diverse group of international clinical and research experts, seeking consensus regarding an...

Fosfomycin has emerged as a potential therapy for multidrug-resistant bacterial infections. In most European countries, the oral formulation is only approved as a 3 g single dose for treatment of uncomplicated cystitis. However, for the treatment of complicated systemic infections, this dose regimen is unlikely to reach efficacious serum and tissue concentrations. This study aims to investigate...

We compared the toxicokinetics of methylmercury in captive common loon chicks during two time intervals to assess the impact of feather growth on the kinetics of mercury. We also determined the oral bioavailability of methylmercury during these trials to test for age-related changes. The blood concentration-time curves for individuals dosed during feather development (initiated 35 days post hat...

TO THE EDITOR—We read with interest the updated guidelines for the management of skin and soft tissue infections from the Infectious Diseases Society of America [1]. Their effort to expand on drug dosing is clear and appreciated. However, we would like to draw attention to a few dosing discrepancies. Table 3 [1] lists regimens for the treatment of intestinal or genitourinary tract infections fo...

Background Metabotropic glutamate receptor 5 has been suggested by many rodent studies to be a promising target for the development of novel analgesic drugs. The lack of approved compounds has prevented proof-of-concept studies in human subjects. Here we describe preclinical and translational studies of the mGlu5 negative allosteric mod-ulator (NAM), fenobam. Fenobam was tested for analgesic ef...

BACKGROUND Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). METHODS/PRINCIPAL FINDINGS MSM and FSW were randomized to daily oral FTC/TD...

Domoic acid (DA), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. However, the toxicokinetics of DA have not been fully evaluated, and information is missing on the disposition of DA following oral exposures at doses that are considered safe for human consumption. In this study, toxicokinetics of DA were investigated in cynomolgus monkeys fo...

This Phase 1, randomized, two-site (United States), double-blind, placebo-controlled study enrolled 18 sexually abstinent men and women. All received a single 300-mg dose of oral tenofovir disoproxil fumarate (TDF) and were then randomized 2:1 to receive single and then seven daily rectal exposures of vaginally-formulated tenofovir (TFV) 1% gel or a hydroxyethyl cellulose (HEC) placebo gel. Blo...

OBJECTIVE To evaluate the effects of oral estradiol given with either oral or intravaginal micronized progesterone (P4) on risk biomarkers for breast cancer in a postmenopausal monkey model. DESIGN This experiment was a two-way crossover study in which 20 ovariectomized adult female cynomolgus macaques were treated (in equivalent doses for women) with oral estradiol (1 mg/d) + oral micronized...

L-683,845 is an orally active inhibitor of human leukocyte elastase. Its disposition was studied in rats and rhesus monkeys after dosing with a 3H- or 14C-labeled compound intravenously at 5 mg/kg and orally at 10 mg/kg. L-683,845 exhibited different pharmacokinetics in these two species. In rats, L-683,845 was well-absorbed after oral dosing, with a maximum concentration of 6 microg/ml at 2 hr...