Subject(s)
Analgesics/therapeutic use , Headache/drug therapy , Pyrazolones , Acetaminophen/adverse effects , Acetaminophen/therapeutic use , Analgesics/adverse effects , Aspirin/adverse effects , Aspirin/therapeutic use , Humans , Ibuprofen/adverse effects , Ibuprofen/therapeutic use , Pyrazoles/adverse effects , Pyrazoles/therapeutic useABSTRACT
51 patients suffering from chronic urinary tract infection were treated from 6 to 12 months with a single evening dose of 100 mg nitrofurantoin. The frequency of re-infection in the treatment period was compared with the same period before onset of therapy. The number of such re-infections was reduced significantly. Side effects of this therapy were substantial lower than after a three-times application per day. Gastrointestinal symptoms could be reduced in more than 50% of the cases by a combined therapy of 100 mg nitrofurantoin and 20 mg vitamin B6.
Subject(s)
Nitrofurantoin/therapeutic use , Urinary Tract Infections/drug therapy , Adolescent , Adult , Bacteriuria/drug therapy , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Pyelonephritis/drug therapy , RecurrenceABSTRACT
2 and 4 g isometronidazole, respectively, were administered to two groups of 6 healthy male volunteers (21-29 years, 62-93 kg). The unchanged compound and its nitro group containing metabolites were measured by HPLC and polarography. Isometronidazole was absorbed rapidly, distributed slowly into peripheral compartments and eliminated with half lives of about 12 h. It was not bound to plasma proteins. On an average 70% (2 g) and 80% (4 g), respectively, were excreted into urine within 48 h both unchanged and in form of at least two more polar and/or water soluble metabolites. Distribution and excretion of isometronidazole were not proportional to dose.
Subject(s)
Metronidazole/analogs & derivatives , Radiation-Sensitizing Agents/pharmacokinetics , Adult , Chromatography, High Pressure Liquid , Humans , Male , Metronidazole/blood , Metronidazole/pharmacokinetics , Metronidazole/urine , Polarography , Radiation-Sensitizing Agents/blood , Radiation-Sensitizing Agents/urine , Tissue DistributionABSTRACT
The metabolism of dihydralazine sulfate was studied in 11 hypertonic patients treated with that drug chronically. The metabolites were identified in urine with gc, dc, and hplc by comparison with synthesized reference compounds. Following metabolites could be verified: acetylated products, oxidation products, hydrazones and products of decomposition. Products resulting from reaction with nitrites could be not detected.
Subject(s)
Dihydralazine/metabolism , Hydralazine/analogs & derivatives , Adult , Aged , Biotransformation , Chromatography, Gas , Chromatography, High Pressure Liquid , Dihydralazine/urine , Female , Humans , Male , Middle AgedSubject(s)
Drug Therapy/methods , Child , Drug Interactions , Drug Therapy, Combination , Humans , KineticsABSTRACT
Age dependence of activity of polymorphic N-acetyltransferase in the fetal human liver was estimated and compared with the hepatic enzyme of adults.
Subject(s)
Acetyltransferases/metabolism , Liver/enzymology , Acetylation , Adolescent , Adult , Child , Female , Gestational Age , Humans , Liver/embryology , Male , Procainamide/metabolismABSTRACT
For the quantitative determination of dihydralazine (1) a derivative with acetylacetone in biological material was formed at pH = 4.9, extracted with n-hexane, and measured gaschromatographically with N-P-FID. Acid labile 1 was hydrolyzed with HCl (1 mol/l) for 24 h. The detection limit was 25 nmol/l plasma. Kinetic studies were performed in 16 patients with essential hypertension under steady-state conditions after the oral application of 50 mg 1. The acetylator phenotype was determined with sulfamethazine. Complete dihydralazine plasma level-time courses were found in only 5 cases. The concentrations were below the detection limit in 4 patients for the whole period. Only single values could be registered in the remaining patients. Maximal plasma levels of the free (58-314 nmol/l) and acid labile 1 (147-367 nmol/l) were reached 20-40 min after the application. The elimination half life was 23-47 min for the free 1, 55-92 min for the acid labile 1. Less than 0.5% of the applied drug were excreted into the 24 h urine in its free form, about 0.4% as acid labile derivatives. No correlation could be found between the acetylator phenotype of the patients and the kinetic behaviour of the drug. Preliminary studies concerning the biliary excretion of 1 after i. m. application in two patients with T-drain showed an accumulation of the free compound with bile/plasma ratios up to 7.4.
Subject(s)
Dihydralazine/metabolism , Hydralazine/analogs & derivatives , Hypertension/metabolism , Acetylation , Adult , Aged , Bile/metabolism , Female , Humans , Kinetics , Male , Middle Aged , PhenotypeABSTRACT
Absolute and relative bioavailability of two commercial calcium dobesilate tablets were evaluated in ten healthy volunteers in a cross-over trial using a newly developed HPLC detection method. Both tablet forms were absorbed completely but very slowly thus leading to a flip-flop kinetics. It could be shown that AUC values derived from flip-flop models were comparable with those of normal i. v. kinetics.
Subject(s)
Benzenesulfonates/metabolism , Calcium Dobesilate/metabolism , Absorption , Adult , Biological Availability , Calcium Dobesilate/administration & dosage , Drug Administration Schedule , Female , Half-Life , Humans , Injections, Intravenous , Kinetics , Male , TabletsABSTRACT
Dihydralazine is a substrate of the human N-acetyltransferase. Therefore the acetylator phenotype could influence the pharmacodynamic response of dihydralazine and/or side effects of this drug. In this study it could be shown that: among patients with dihydralazine incompatibility slow acetylators preponderated; the risk of early side effects was higher in females than in males; and the ratio of fast/slow acetylators was higher in dihydralazine treated patients than in patients treated with other antihypertensives. Dihydralazine should be given very cautiously to female hypertonic patients that are slow acetylators.