ABSTRACT
A patient with newly-diagnosed HIV infection and biopsy-proven cerebral toxoplasmosis was treated with sulphadiazine and pyrimethamine. Despite adequate hydration and daily examination of urine for sulphadiazine crystals obstructive uropathy due to bilateral ureteric stones with hydronephrosis occurred, resulting in rapid onset renal failure. Sulphadiazine was discontinued and clindamycin was substituted. With intravenous fluid hydration and bilateral nephrostomies the urolithiasis resolved. This case serves to remind clinicians of the need for vigilance when treating cerebral toxoplasmosis with sulphadiazine, in order to avoid this potentially serious complication of treatment.
Subject(s)
Antiprotozoal Agents/adverse effects , HIV Infections/complications , Renal Insufficiency/chemically induced , Sulfadiazine/adverse effects , Toxoplasmosis, Cerebral/drug therapy , Ureteral Obstruction/complications , Urinary Calculi/complications , Antiprotozoal Agents/administration & dosage , Fluid Therapy , Humans , Middle Aged , Nephrostomy, Percutaneous , Pyrimethamine/administration & dosage , Renal Insufficiency/diagnosis , Sulfadiazine/administration & dosage , Ureteral Obstruction/chemically induced , Ureteral Obstruction/diagnosis , Urinary Calculi/chemically induced , Urinary Calculi/diagnosisABSTRACT
Packages that provided stability (less than a 10% loss in potency) of a moisture sensitive compound (PGE-7762928) in tablet form at accelerated conditions for 6 months were identified. The equilibrium moisture content of the tablets at 25 degrees C/60%RH, 30 degrees C/60%RH and 40 degrees C/75%RH were 2.3,2.4, and 2.9%, respectively. The tablet equilibrium moisture content, degradation rate of unpackaged product, and the moisture barrier properties of the packages were used to predict the stability of the packaged product. The physical and chemical stability (HPLC assay) of the products were measured after 2,4,6,8,12, and 24 weeks at ICH conditions. The Containers-Permeation(1) of polyvinyl chloride blisters, cyclic olefin blisters, aclar blisters, cold-form aluminum blisters was 0.259, 0.040, 0.008 and 0.001 mg per blister per day, respectively. At 6 months at 40 degrees C/75%RH, the percent active was 84% in polyvinyl chloride blisters, 91% in cyclic olefin blisters, 97% in aclar blisters, 100% in cold-form aluminum blisters and 99% in an high density polyethylene bottle with a foil induction seal. The stability results for the packaged product were fairly consistent with the predictions based on the moisture sensitivity of the product and the moisture barrier properties of the respective package. To gain a better prediction, the flux value determined by the Containers-Permeation procedure was adjusted for the internal moisture concentration of the blister.