No abstract

Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo.

Concurrent administration of SJW had no significant effect on the single-dose pharmacokinetics of prednisone or metabolic prednisolone in male subjects.

This study evaluated the pharmacokinetics of topical creams containing 15% paromomycin ("paromomycin alone") and 15% paromomycin plus 0.5% gentamicin (WR 279,396) in patients with cutaneous leishmaniasis. The investigational creams were applied topically to all lesions once daily for 20 days. Plasma samples were analyzed for simultaneous quantitation of paromomycin and gentamicin isomers and total gentamicin. Pharmacokinetic parameters for gentamicin could not be calculated because detectable levels were rarely evident. After one application, the paromomycin area under the concentration-time curve from 0 to 24 h (AUC 0 -24 ) was 2,180 ؎ 2,621 ng · h/ml (mean ؎ standard deviation [SD]) for the paromomycin-alone group and 975.6 ؎ 1,078 ng · h/ml for the WR 279,396 group. After 20 days of application, the paromomycin AUC 0 -24 and maximum concentration of drug (C max ) were 5 to 6 times greater than those on day 1 for both treatment groups. For the paromomycin-alone group, the AUC 0 -24 was 8,575 ؎ 7,268 ng · h/ml and the C max was 1,000 ؎ 750 ng/ml, compared with 6,037 ؎ 3,956 ng · h/ml and 660 ؎ 486 ng/ml for the WR 279,396 group, respectively. Possibly due to large intersubject variability, no differences (P > 0.05) in the AUC 0 -24 or C max were noted between treatment or between sites on day 1 or 20. The percentage of dose absorbed on day 20 was 12.0% ؎ 6.26% and 9.68% ؎ 6.05% for paromomycin alone and WR 279,396, respectively. Paromomycin concentrations in plasma after 20 days of application were 5 to 9% of those after intramuscular administration of 15 mg/kg of body weight/day to adults for the systemic treatment of visceral leishmaniasis. Effective topical treatment of cutaneous leishmaniasis appears to be possible with limited paromomycin and gentamicin systemic absorption, thus avoiding drug accumulation and toxicity. (The work described here has been registered at ClinicalTrials.gov under registration no. NCT01032382 and NCT01083576.) A combination of paromomycin and gentamicin in a topical cream formulation (WR 279,396) is being investigated for the treatment of uncomplicated cutaneous leishmaniasis (CL), a parasitic infection caused by the bite of a sandfly that results in an ulcerated skin lesion frequently 2 to 5 cm in diameter (1). Leishmaniasis has been found in more than 90 countries worldwide (2). It is estimated that the incidence of CL ranges from 0.7 million to 1.2 million cases annually (2). In the United States, CL has been found in southern Texas along the Mexican border (3) and in travelers returning from areas of endemicity (4). In the U.S. military, more than 3,100 cases of CL have been parasitologically confirmed since April 2003 at the Leishmania Diagnostics Laboratory at the Walter Reed Army Institute of Research. Although CL ultimately self-cures, the infection can create substantial morbidity due to the continued presence of a skin ulcer and the psychological impact of disfigurement (5).Currently, there are no FDA-approved drugs for the treatment of any form of CL in the United Stat...

The purpose of this study was to evaluate the pharmacokinetics of ketamine in mature Holstein cows following administration of a single intravenous (i.v.) dose. Plasma and milk concentrations were determined using a high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following i.v. administration, plasma T(max) was 0.083 h and plasma C(max) was 18,135 ± 22,720 ng/mL. Plasma AUC was 4484 ± 1,398 ng·h/mL. Plasma t(½β) was 1.80 ± 0.50 h and mean residence time was 0.794 ± 0.318 h with total body clearance of 1.29 ± 0.70 L/h/kg. The mean plasma steady-state volume of distribution was calculated as 0.990 ± 0.530 L/kg and volume of distribution based on area was calculated as 3.23 ± 1.51 L/kg. The last measurable time for ketamine detection in plasma was 8.0 h with a mean concentration of 24.9 ± 11.8 ng/mL. Milk T(max) was detected at 0.67 ± 0.26 h with C(max) of 2495 ± 904 ng/mL. Milk AUC till the last time was 6593 ± 2617 ng·h/mL with mean AUC milk to AUC plasma ratio of 1.99 ± 2.15. The last measurable time that ketamine was detected in milk was 44 ± 10.0 h with a mean concentration of 16.0 ± 9.0 ng/mL.