ABSTRACT
Grapefruit juice has been reported to markedly improve the bioavailability of triazolam, midazolam, terfenadine, cyclosporine and several dihydropyridine calcium channel blockers including felodipine, nifedipine, nitrendipine and nisoldipine. Because these drugs are metabolized by the hepatic cytochrome P450 isozyme (CYP) 3A4, the inhibitory effect of grapefruit juice is thought to results from inhibition of CYP3A4. In this study, our aim was to investigate the effects of grapefruit juice on plasma concentrations of diazepam. Eight healthy male and female subjects participated in this study. Oral (5 mg) diazepam was administered with either 250 ml water and grapefruit juice. Blood samples were collected for a 24 h period, and whole blood concentrations of diazepam were measured enzyme immunoassay. The mean AUC(0-24) of diazepam was increased 3.2-fold (P < 0.001) and Cmax was increased 1.5-fold (P < 0.05) by the grapefruit juice. Grapefruit juice postponed the tmax of diazepam from 1.50 h to 2.06 h (P < 0.01).
Subject(s)
Beverages , Citrus , Diazepam/pharmacokinetics , Adult , Biological Availability , Cross-Over Studies , Cytochrome P-450 Enzyme System/physiology , Female , Humans , MaleSubject(s)
Nitrates/pharmacology , Nitrites/metabolism , Saliva/metabolism , Adolescent , Adult , Aging , Child , Diet , Female , Humans , Male , Middle Aged , Parotid Gland/drug effects , Parotid Gland/metabolism , Saliva/drug effects , Sex Characteristics , Smoking/metabolismABSTRACT
The effect of vasoactive intestinal polypeptide (VIP) on the contractile activity of the urinary bladder was investigated in the rat. VIP caused a weak contraction and a small potentiation of carbachol- and acetylcholine-induced contractions. The present results may provide the evidence that VIP could be a modulator in the urinary bladder.
Subject(s)
Muscle Contraction/drug effects , Muscle, Smooth/physiology , Urinary Bladder/physiology , Vasoactive Intestinal Peptide/pharmacology , Acetylcholine/pharmacology , Animals , Carbachol/pharmacology , In Vitro Techniques , Male , Muscle, Smooth/drug effects , Rats , Urinary Bladder/drug effects , Vasoactive Intestinal Peptide/physiologyABSTRACT
The effects of a 7 days chemotherapy with ciprofloxacin or ofloxacin on the cellular and humoral immune responses in albino mice were studied. The non-toxic doses of the drugs (10 or 30 mg/kg/day) were used. The delayed-type hypersensitivity reaction to sheep blood cells and skin biopsy were evaluated for cellular immune response. The complement fixation method was applied for the determination of the humoral immune response. Both drugs increased the cellular and humoral immune responses.
Subject(s)
Antibody Formation/drug effects , Ciprofloxacin/pharmacology , Immunity, Cellular/drug effects , Ofloxacin/pharmacology , Animals , Complement Fixation Tests , Hypersensitivity, Delayed , MiceABSTRACT
The effects of nitrendipine on stress-induced acute gastric lesions were investigated in rats. Intraperitoneally injected nitrendipine (8, 16, or 32 mg/kg) given 30 min before stress, dose-dependently prevented gastric glandular ulceration. The anti-ulcer effects of nitrendipine were not reversible by indometacin or dexamethasone. These results suggest that calcium is important in gastric pathophysiology and that the proof of gastroprotective effects of calcium channel blockers is of great value in the development of new and improved therapies for treatment and prevention of gastric ulcers in humans.
Subject(s)
Nitrendipine/therapeutic use , Peptic Ulcer Hemorrhage/prevention & control , Stomach Ulcer/prevention & control , Stress, Physiological/complications , Animals , Cold Temperature , Dexamethasone/pharmacology , Female , Immobilization , Indomethacin/pharmacology , Male , Peptic Ulcer Hemorrhage/etiology , Rats , Stomach Ulcer/complications , Stomach Ulcer/etiologyABSTRACT
It is well known that infection-induced stones (apatite, struvite), uric acid and cystine calculi in the urinary tract can be managed by the use of certain chemical solutions. We investigated the effects of various acidic and alkaline solutions on the rabbit urothelium. Acidic solutions (pH: 4.2) caused more urothelial injury as compared to alkaline solutions (pH: 7.6). Ureteral injury was more severe than the bladder injury. Magnesium-containing solutions caused less injury to the urothelium.
Subject(s)
Carbonates/toxicity , Citrates/toxicity , Magnesium Oxide/toxicity , Ureter/drug effects , Urinary Bladder/drug effects , Urinary Calculi/therapy , Animals , Calcium Carbonate/toxicity , Drug Combinations , Female , Hydrogen-Ion Concentration , Male , Rabbits , Therapeutic IrrigationABSTRACT
Analgesic and anti-inflammatory effects of N-(p-ethoxyphenyl)-2,6-dihydroxybenzamide (1), N-(p-ethoxyphenyl)-2,6-diacetoxybenzamide (2), N-(p-ethoxyphenyl)-2,5-dihydroxybenzamide (3), and N-(p-ethoxyphenyl)-2,5-diacetoxybenzamide (4) have been investigated in mice and rats. The analgesic effect of 2 on acetic acid-induced writhing was found to be stronger than that of aspirin, whereas that of 1, 3, and 4 was weaker than that of aspirin. In inflammatory studies, 1-4 showed inhibition of formaldehyde-induced paw swelling (edema). The effects of 1-3 were more potent than that of aspirin, 1 being the most potent. The potency of 4 was almost equal to that of aspirin.
Subject(s)
Anilides/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anilides/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Biological Availability , Male , Mice , Rats , Structure-Activity RelationshipABSTRACT
Kallidin and bradykinin produce a biphasic response, contraction followed by relaxation on the isolated guinea-pig tracheal muscle. Two population of receptors appear to regulate the action of kinins on the trachea. Receptors on the epithelium seem to release chemical mediators that control the relaxation response. The question whether similar or different receptors modulate contraction of the smooth muscle may be answered by the use of appropriate antagonists. The occurrence of kinins in bronchial lavage of patients with asthma raises the question of the source of tissue kallikrein involved in the formation of kallidin. We have identified immunoreactive tissue kallikrein in the submucous glands of the trachea.
