Shaefer Ms

Hepatic failure associated with imipramine therapy

Imipramine, a widely used antidepressant, has rarely been associated with hepatic abnormalities. In the majority of reported cases, hepatic effects have been transient and readily reversible on discontinuation of the drug. We cared for an 11‐year‐old boy with hepatic failure and massive cell necrosis which followed treatment with imipramine for enuresis. This therapy led to fulminant hepatic failure and subsequent liver transplantation.

Blind Comparison of Patient Preference for Flavored Colestid Granules and Questran Light

OBJECTIVE: To compare the sensory and mixability characteristics of Flavored Colestid Granules (a new colestipol formulation) with Questran Light (the most recent cholestyramine formulation). METHODOLOGY: Seventy-two nonsmoking adults between the ages of 25 and 64 years were enrolled in the study. Subjects assessed the sensory and mixability characteristics of each product in chilled bottled water and orange juice after at least a one-hour fast. Products were administered in a double-blind, randomized fashion. The sensory characteristics that were rated included overall rating, aftertaste, appearance, aroma, color, consistency, flavor, sweetness, mouthfeel, and thickness. Each characteristic was rated with a nine-point hedonic scale. Mixability of the products was assessed on a five-point scale. Subjects also were asked to choose which product they preferred as to sensory and mixability characteristics in each vehicle. RESULTS: Fifty-three of the 72 subjects preferred the sensory characteristics of Flavored Colestid Granules in water (p<0.001). Questran Light was preferred by 61 subjects when mixed in orange juice (p<0.001). The sensory characteristic rating scores also supported subject preferences for Flavored Colestid Granules in water and Questran Light in orange juice. Mixability of Flavored Colestid Granules was rated significantly better (p<0.001) than Questran Light in water. There was no significant difference for mixability between the products in orange juice. CONCLUSIONS: Questran Light was significantly preferred on a sensory basis when mixed in orange juice. Flavored Colestid Granules was significantly preferred over Questran Light for both sensory and mixability characteristics with water as the vehicle.

Current Topics in Immunotherapy and the Role of the Pharmacist on a Solid Organ Transplant Service

Solid organ transplantation has become a well‐accepted therapy for the treatment of end‐stage disease of the liver, heart, kidney, and pancreas. The development of highly effective immunosuppressant drugs has led to major improvements in graft and patient survival over the last decade. In spite of this success the perfect immunosuppressive drug has yet to be discovered. Currently available agents have numerous short‐term and, more disturbingly, long‐term toxicities. This has led to the use of triple‐ and quadruple‐drug regimens in an attempt to maintain good graft and patient survival rates with less toxicity. Multiple‐drug combinations have questionable benefits compared to double‐drug regimens containing cyclosporine and prednisone. With the advent of new immunosuppressant drugs, it will be important to perform randomized, controlled trials to assess their efficacy and toxicities in comparison with current regimens. Pharmacists who work with solid organ transplant teams can function as pharmacotherapists and provide skills such as pharmacokinetic and pharmacodynamic drug monitoring. In addition, they can become involved with clinical and laboratory‐based research to assess the properties of conventional and newly developed immunosuppressive agents.

Evaluation of the pharmacokinetic interaction between cimetidine or famotidine and cyclosporine in healthy men.

Objective: To investigate the potential interaction between cimetidine or famotidine and cyclosporine in healthy men. Design: All subjects received oral cyclosporine at baseline, after the first week of 1 histamine2 (H2)-blocker, and a third time after a 1-week washout plus 1 week of the second H2-blocker. Blood samples were collected just before each dose of cyclosporine and for up to 36 hours afterward for pharmacokinetic analysis. Setting: A college of pharmacy in a university teaching hospital. Participants: The study population consisted of 8 healthy men at least 19 years of age. Main Outcome Measures: Cyclosporine concentrations in whole blood were measured using a polyclonal fluorescence polarization immunoassay. Cyclosporine pharmacokinetic parameters during each of the 3 treatment periods were compared. Results: The average times to maximum cyclosporine concentrations were similar between baseline (3.2 h), cimetidine (2.9 h), and famotidine (3.6 h) dosing periods. There were no significant differences in area under the curve, half-life, or maximum concentration during the 3 dosing periods. Conclusions: Neither cimetidine or famotidine produced a significant change in the pharmacokinetics of single-dose oral cyclosporine in healthy men.