ABSTRACT
The objective of this study was to evaluate the pharmacokinetics, pharmacodynamic response, and safety of single intravenous (i.v.), intramuscular (i.m.), and subcutaneous (SQ) doses of interferon alfa-n3. Six healthy adults received 10 million units of i.v., i.m., and SQ interferon alfa-n3 in a randomized three-period crossover fashion. Serum interferon alfa-n3 concentrations and 2'-5'-oligoadenylate synthetase (2-5[A] synthetase) activity in peripheral blood mononuclear cells were determined after each dose. Extravascular administration significantly increased mean serum interferon alfa-n3 AUC values (1152 +/- 214, 944 +/- 209, and 576 +/- 188 U.h/mL, p < 0.001, with SQ, i.m., and i.v. administration, respectively) and 2-5(A) synthetase activity at 36 and 48 hours after dosing. Mild to moderate flu-like symptoms were reported by all 6 subjects, with no route-related difference in type or incidence. Interferon alfa-n3 is generally well tolerated by the i.v., i.m., and SQ routes, with i.m. and SQ administration maximizing serum exposure and 2-5(A) synthetase activity.
Subject(s)
2',5'-Oligoadenylate Synthetase/blood , Interferon-alpha/pharmacokinetics , Adolescent , Adult , Cross-Over Studies , Female , Humans , Injections, Intramuscular , Injections, Intravenous , Injections, Subcutaneous , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Male , Middle AgedABSTRACT
As part of a large multicenter surveillance study of captopril, 975 hypertensive patients aged 65 years or older were treated, 418 of whom received the drug for at least 12 months. Blood pressure was lowered from an entry level of 193/105 +/- 30/16 (mean +/- SD) to 159/88 +/- 25/12 mm Hg, and side effects were infrequent. During treatment, renal function was undisturbed in the majority of patients. The frequency of clinically evident hypotensive episodes did not differ from that found in the total study population, suggesting that in this age group, despite the reduction in blood pressure, cerebral perfusion was maintained. This experience suggests that captopril can be used for the treatment of the elderly hypertensive patient.
Subject(s)
Captopril/administration & dosage , Hypertension/drug therapy , Aged , Blood Pressure , Clinical Trials as Topic , Drug Administration Schedule , Female , Humans , Hypertension/physiopathology , Hypertension, Malignant/drug therapy , Hypertension, Malignant/physiopathology , Hypertension, Renal/drug therapy , Hypertension, Renal/physiopathology , Hypertension, Renovascular/drug therapy , Hypertension, Renovascular/physiopathology , Male , Patient ComplianceABSTRACT
The differing sensitivities of the gallbladder and pancreas to graded doses of CCK have been claimed as important in normal digestive events. As both secretin and CCK are thought to be released in response to normal feeding, we have reexamined the sensitivities of the gallbladder and pancreas to graded increases of CCK with a constant secretin background. Under such conditions the increase in output of pancreatic trypsin and bile salt occurred simultaneously, the dose-response curves being almost superimposable. Thus, under conditions more closely approaching normal postcibal events, the previously described differing sensitivities of the pancreas and gallbladder were not observed.
