ABSTRACT
The primary objective of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of tasosartan and atenolol administered alone and concomitantly under steady-state conditions in 17 patients ages 18 to 65 years diagnosed with stage 1 to 2 essential hypertension. After a 3- to 14-day qualification period, all patients received placebo tasosartan on days--1 through 5 and 25 through 34, atenolol alone (50 mg) on days 1 through 5, atenolol (50 mg) + tasosartan (50 mg) on days 6 through 19, and tasosartan (50 mg) alone on days 20 through 24. A PK and PD evaluation of atenolol alone was performed on study day 5. On study day 19, PK and PD of both tasosartan and atenolol were assessed. PK and PD evaluation for tasosartan alone was assessed on study day 24. The coadministration of atenolol + tasosartan did not affect the pharmacokinetics of tasosartan, its major metabolite (enoltasosartan), or atenolol when compared with tasosartan or atenolol administered separately. For area under the change in diastolic blood pressure curve, the reduction was significantly greater after tasosartan + atenolol compared with that after atenolol alone (336 +/- 85 and 190 +/- 71 mmHg.24 h; p < 0.05 for combination and atenolol alone, respectively; mean +/- SEM). Combination therapy also caused a maximal reduction in diastolic blood pressure that is significantly more than with monotherapy with atenolol (-27 +/- 2 mmHg and -20 +/- 2 mmHg, respectively, p < 0.05). The additive effects of tasosartan and atenolol in decreasing diastolic blood pressure may provide a rationale for combination antihypertensive therapy.
Subject(s)
Adrenergic beta-Antagonists/pharmacology , Angiotensin II/metabolism , Angiotensin Receptor Antagonists , Atenolol/pharmacology , Hypertension/metabolism , Pyrimidines/pharmacology , Tetrazoles/pharmacology , Adolescent , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/pharmacokinetics , Adult , Aged , Atenolol/administration & dosage , Atenolol/pharmacokinetics , Drug Synergism , Humans , Hypertension/drug therapy , Middle Aged , Pyrimidines/administration & dosage , Pyrimidines/pharmacokinetics , Single-Blind Method , Tetrazoles/administration & dosage , Tetrazoles/pharmacokineticsABSTRACT
An adult drug abuser with endocarditis due to a group II Staphylococcus aureus developed the staphylococcal scalded skin syndrome (SSSS). Studies of the patient's immune function found cell-mediated immunity (CMI) to be essentially normal; thus, previous suggestions that deficient CMI is required in adults who develop SSSS seem unfounded. Pathogenesis, diagnosis, and therapy of SSSS and its differentiation from drug-induced hypersensitivity reaction are discussed in detail.
Subject(s)
Staphylococcal Infections/diagnosis , Stevens-Johnson Syndrome/diagnosis , Adult , Aged , Diagnosis, Differential , Drug Hypersensitivity/diagnosis , Female , Humans , Immunity, Cellular , Male , Middle Aged , Staphylococcal Infections/immunology , Staphylococcal Infections/pathology , Stevens-Johnson Syndrome/immunology , Stevens-Johnson Syndrome/pathology , Substance-Related Disorders/complications , SyndromeABSTRACT
Sulfasalazine hepatotoxicity has been poorly documented in the literature. We report a case of a young female with inflammatory bowel disease who developed severe hepatotoxicity as part of a systemic hypersensitivity reaction to sulfasalazine. The clinical, biochemical, and histopathological features resemble those of sulfonamide-induced hepatic injury. Although rare, our case as well as previous reports indicate the serious nature of the illness.
