Estimation of neonatal exposure after accidental ingestion of lufenuron in a breastfeeding mother.

A case of accidental anti-flea preparation (lufenuron) ingestion by a breastfeeding mother is reported. An estimation of infant exposure level was calculated based on the highest level measured. The breastfed infant was exposed to an average lufenuron dose of 0.032 mg/kg/day, which is only 3% of a reported acute overdose. No adverse effects were reported during 7 months of follow-up. Breastfeeding should be considered cautiously after consultation with a regional poison center in cases of accidental ingestion of this drug by a breastfeeding mother. The infant should be monitored for potential adverse effects.

Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration.

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.

Pharmacokinetics of clomipramine in dogs following single-dose and repeated-dose oral administration.

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following single-dose and repeated-dose oral administration at various dosages. ANIMALS: 9 male and 9 female Beagles. PROCEDURES: Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Dose-related accumulation was detected following repeated-dose administration. Accumulation ratios after administration of clomipramine at dosages of 1, 2, and 4 mg/kg twice daily were 1.4, 1.6, and 3.8, respectively, for clomipramine and 2.1, 3.7, and 7.6, respectively, for desmethylclomipramine. Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated-dose administration but remained short in all groups (< or = 4 hours). Steady state was reached within 4 days in all animals. Ratios of the areas under the concentration versus time curves from time 0 to 12 hours for clomipramine and desmethylclomipramine were 3.9, 3.1, and 1.5 after repeated administration at dosages of 1, 2, and 4 mg/kg every 12 hours, respectively. Areas under the concentration versus time curve, mean residence times, and terminal half-lives were not significantly different between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated administration of clomipramine results in higher concentrations of clomipramine than desmethylclomipramine in dogs.

Determination of Lufenuron in canine skin layers by radioluminography.

In a bioavailability study in dogs we investigated the quantity of [14C]-Lufenuron and its metabolites in the skin by radioluminography. Two Beagle dogs were orally administered 10 mg [14C]-Lufenuron per kg body weight. 21 days later they were euthanized. Skin specimens were taken at 6 different sites. Sections of these skin specimens were exposed on a phosphorus imaging plate and the radiolabeled Lufenuron content visualized. Radioluminographical analysis showed that [14C]-Lufenuron appeared in the subcutaneous layer of the skin. We did not discover any activity on the skin surface.

Marketing planning for ambulatory care: twelve key steps.

Effective health care marketing begins with an excellent product that addresses the needs and preferences of key consumers of services. Sophisticated marketing proceeds from an understanding that healthcare "markets" now include physician, payer, and patient components. An ambulatory cancer center can meet the needs of all three of these crucial components. This article describes key characteristics of an ambulatory cancer center and shows how the ambulatory center addresses important concerns of physicians, payers, and patients.