Cost advantages of oral drug therapy for managing cytomegalovirus disease.

Cost advantages of the oral route of drug therapy administration over the intravenous route for managing cytomegalovirus (CMV) disease are described. The overall costs usually are lower for the oral route of administration than for the intravenous route, although the cost to the patient depends on insurance coverage. Other advantages of the oral route include greater safety and convenience, which may improve patient adherence and quality of life. In patients with acquired immunodeficiency syndrome (AIDS), the use of oral ganciclovir instead of intravenous ganciclovir to treat the maintenance phase of CMV retinitis reduced the incidence of neutropenia and sepsis, outpatient and inpatient resource use, and costs. Oral therapy also improved patient quality of life. A cost-effectiveness model for liver transplant recipients found that CMV prophylaxis is warranted for all patients, ganciclovir is preferred over CMV immune globulin i.v. and oral acyclovir for prophylaxis, and the oral route of administration is more cost-effective than the intravenous route for ganciclovir. Valganciclovir, the oral prodrug of ganciclovir, was not included in this model. Oral maintenance therapy is usually cost-effective, safer, and more convenient than intravenous therapy in the management of CMV.

Early experience with sirolimus in lung transplant recipients with chronic allograft rejection.

BACKGROUND: Chronic lung allograft rejection, commonly manifest as obliterative bronchiolitis (OB/BOS), hinders long-term survival after lung transplantation (LT). OB/BOS is traditionally treated with augmented immunosuppression and results in short-term stabilization in pulmonary function for most patients. However, peribronchiolar fibroproliferation and airway obstruction usually recur despite initial improvements seen with increases in immunosuppression. In this observational, uncontrolled study, the effect of sirolimus, a novel immunosuppressant with anti-proliferative activity, was assessed in LT patients with OB/BOS. METHODS: Between June 1999 to November 2000, LT recipients with newly diagnosed or progressive OB/BOS received sirolimus in combination with a calcineurin inhibitor (CI) and prednisone. Pulmonary function, laboratory data and adverse effects were monitored for the first 24 weeks of therapy. RESULTS: Sirolimus was utilized in 12 LT recipients with OB/BOS. After drug initiation, 58% of patients required a reduction in CI dose to maintain appropriate CI trough concentrations. Despite CI dose reduction, serum creatinine rose in 75% of patients. Unexpected adverse effects included anemia of chronic disease (100%), edema (50%) and malignancy (17%). For the group, the rate of change in FEV(1) and FEF(25%-75%) was unchanged with sirolimus, but individual responses varied. CONCLUSIONS: For the group, the decline in pulmonary function was not affected by the addition of sirolimus. However, among individuals with rapidly declining pulmonary mechanics, sirolimus resulted in stabilization or improvement in pulmonary function. Significant adverse effects resulted from combination sirolimus plus CI therapy. Until optimal dosing strategies and a more complete adverse effect profile are established, combination therapy should be utilized cautiously in these patients.

Modifications in cyclosporine (CsA) microemulsion blood concentrations by olestra.

OBJECTIVE: Determine whether olestra alters the absorption of cyclosporine microemulsion in pediatric renal transplant recipients. DESIGN: Prospective, open-label, crossover pharmacokinetic study. SETTING: General clinical research center in a university medical setting providing tertiary care. PARTICIPANTS: Seven pediatric-adolescent renal transplant recipients, ages 9 to 18, 5 to 24 months post-transplant with mean serum creatinine of 0.9 mg/dL (range, 0.7-1.6 mg/dL). METHODOLOGY: Patients participated in 2 study periods: 1. Patients were given their usual dose of Neoral (Novartis Pharmaceuticals Corporation, East Hanover, NJ) without olestra, 2. patients were given their usual dose of Neoral combined with 0.35 g/kg (maximum of 16 g of olestra or approximately 2 ounces of Lays WOW [Frito Lay, Plano, TX] potato chips). The 2 study periods were separated by a minimum 7-day washout period. CsA blood concentrations were obtained at 1, 2, 3, 4, 6, 8, and 12 hours after drug administration. RESULTS: Each patient in the study had a consistent decrease in area under the curve (AUC) when given olestra along with their usual dose of Neoral, compared with giving Neoral alone (5,018 ng*hr/mL versus 4,086 ng*hr/mL; P <.001). There also was a decrease in maximum concentration (Cmax) when Neoral was given with olestra compared with giving Neoral alone (1,202 ng/mL versus 876 ng/mL; P =.015). There was no statistical difference in the mean elimination rate or the trough values for both regimens (half-life 4.767 hours versus 4.771 hours and trough levels of 143 ng/mL versus 124 ng/mL). CONCLUSION: Olestra decreases total CsA exposure in pediatric renal transplant recipients. The noted decrease in AUC was not adequately predicted by CsA trough values which could lead to rejection episodes in the clinical setting.