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Biomedical subjects

A Karim

Publications and source records attributed to A Karim.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Metabolism of actisomide in the dog, monkey and man: a novel rearrangement of N-dealkylated metabolites.

The metabolism of actisomide, a novel antiarrhythmic agent, was studied in the dog, monkey and man and was found to be more extensive in the monkey than in the dog or man. The major metabolites identified were a piperidinyl hydroxylated metabolite, the mono-N-dealkylated, cyclized and piperidine hydroxylated metabolite, and the cyclized and mono-N-dealkylated metabolite. Excretion of the parent drug was higher in urine than in feces in the dog, but in the monkey and man, urinary and fecal excretion of actisomide was similar. In all species the metabolites were primarily excreted in feces.

Adult↗
PubMedDate not supplied

Cardiac drug and psychotropic drug interactions: significance and recommendations.

Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist and primary care physician, as well as for the psychiatrist. There has been an explosive use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward poly-pharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models/paradigms for predicting potential drug interactions--e.g., the Cytochrome p450 schema. This paper describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician. Since the majority of the original clinical trials, either for cardiac medications or psychotropic drugs, do not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as "guinea pig," and through subsequent reporting.

Cardiovascular Agents↗
PubMedDate not supplied

Cardiac drug and psychotropic drug interactions: significance and recommendations.

Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist, primary care physician, and psychiatrist. There has been an explosion in the use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward polypharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models and paradigms for predicting potential drug interactions-the cytochrome P450 schema. This article describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database, and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician (Appendix). Because the majority of the original clinical trials, either for cardiac medications or for psychotropic drugs, did not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as "guinea pig" and through subsequent reporting.

Animals↗
PubMedDate not supplied

VEB-1-like extended-spectrum beta-lactamases in Pseudomonas aeruginosa, Kuwait.

Two clinical Pseudomonas aeruginosa isolates from patients in intensive care units in Kuwait were resistant to expanded-spectrum cephalosporins and showed a synergistic effect between ceftazidime and clavulanic acid. This is the first report of extended-spectrum enzymes from nosocomial isolates from the Middle East.

Amino Acid Sequence↗
PubMedDate not supplied

Valsalva retinopathy-like hemorrhage associated with combined trabeculotomy-trabeculectomy in a patient with developmental glaucoma.

This case describes valsalva retinopathy-like hemorrhage in a patient with developmental glaucoma who underwent primary combined trabeculotomy-trabeculectomy. A 12-year-old boy with developmental glaucoma in both eyes developed shallow anterior chamber following combined trabeculotomy-trabeculectomy in his right eye. He underwent air injection for reformation of the anterior chamber under general anesthesia. Following reformation of the anterior chamber on the 5th postoperative day, examination of the patient revealed valsalva retinopathy-like hemorrhage. The patient was treated with betamethasone and cyclopentolate in the postoperative period, and was followed by complete absorption of the retinal hemorrhages with retention of normal visual acuity. Valsalva retinopathy-like hemorrhage may occur with valsalva maneuver during general anesthesia.

Anesthesia, General↗
PubMedDate not supplied

Species differences in the metabolism and disposition of spironolactone.

The absorption, excretion and metabolism of [22-14C]spironolactone was compared in Charles River rats, beagle dogs and rhesus monkeys. The drug was administered at the fixed dose of 5 mg/kg po and iv. From the po/iv ratios of the areas under the plasma radioactivity-time curves, the gastrointestinal absorption of the drug was estimated to be 82% in the rat, 62% in the dog, and 103% in the monkey. The absolute bioavailability of a pharmacologically active metabolite, canrenone, was 57% in the dog and 48% in the monkey. Spironolactone was extensively metabolized in all three species and differences existed in the composition of the metabolites in their plasma, urine, and feces. The amount of radioactivity that was excreted in the urine and feces of all three species was similar after either po or iv administration of the drug. The cumulative average excretion of radioactivity in the urine as percentage of the po dose in 6 days was 4.69% in the rat (N = 5), 18.5% in the dog (N = 3), and 46.0% in the monkey (N = 3). In the feces, the corresponding excretion values were 74.2, 69.3 and 40.1%, respectively. Canrenone excretion in the urine constituted 0.65% of the po dose in the rat, 0.82% in the dog, and 5.86% in the monkey, whereas the excretion of total fluorogenic metabolites constituted 1.1, 1.9, and 12.1% respectively. Comparison of animal data with those published for humans indicated that the disposition and metabolism of spironolactone in the rhesus monkey, rather than those in the rat or the dog, was closest to that in man.

Animals↗
PubMedDate not supplied

Spironolactone metabolism in man studied by gas chromatography-mass spectrometry.

Gas chromatography-mass spectrometry was used to identify metabolites of spironolactone in human blood and urine. In three healthy men about 20% of the radioactivity was excreted in the urine within 24 hr after an oral dose of [20-3H]spironolactone (200 mg + 200 muCi). About half of this radioactivity was extracted with chloroform at pH 3 and from this extract four stable metabolites were isolated by use of column and thin-layer chromatography. Two of these were the previously identified metabolites, canrenone (VII; 2.9% of dose) and the 6beta-hydroxy-sulfoxide (X; 1.8% of the dose). The remaining were the new metabolites, 15alpha-hydroxycanrenone (XI; 0.8% of dose) and the 6beta-hydroxy-thiomethyl derivatives (VI; 0.5% of dose). The principal water-soluble urinary metabolite was canrenoate ester glucuronide (XII; 4.5% of dose). In the 24- to 32-hr pooled serum, canrenone (VII) was the principal metabolite in the organic-extractable fraction; VI was present in appreciable amounts but X and XI were present at extremely low levels.

Canrenone↗
PubMedDate not supplied

Pharmacokinetics of disopyramide in the dog. Importance of mono-N-dealkylated metabolite kinetics in assessing pharmacokinetic modeling of the parent drug.

The antiarrhythmic drug disopyramide (DP) is metabolized to the mono-N-dealkylated compound (MND) and to the pyrrolidone derivative (PYR). This study examines the detailed pharmacokinetic characteristics of DP and MND when given simultaneously or separately to dogs. DP and MND were both relatively well absorbed and showed similar pharmacokinetic characteristics. However, the amount of PYR relative to MND as judged by the area under the plasma concentration-time curves (AUC) following oral or iv administration was much greater with DP than with MND. These findings were also supported by the urinary excretion values where the PYR/MND ratio with DP was much greater than with the MND administration. For an explanation of this phenomenon, plasma concentration-time curves for DP, MND, and PYR were simultaneously analyzed assuming various pharmacokinetic models. The plasma levels of these compounds were best described when nonlinear kinetics were assumed for conversion of MND to PYR.

Absorption↗
PubMedDate not supplied

Pharmacokinetics and steady-state myocardial uptake of disopyramide in the dog.

The pharmacokinetics and steady-state myocardial uptake of the antiarrhythmic drug disopyramide (DP) were determined in dogs after oral or intravenous administration of [14C]disopyramide phosphate. DP was absorbed rapidly and its absolute oral bioavailability was about 70%. Significant dose-dependent kinetics were not apparent after 7.5- to 30-mg/kg po doses. Plasma half-lives of DP were about 2.9 and 1.2 hr after the po and iv doses, respectively. DP and its N-dealkylated metabolites were largely excreted in the urine and their composition was qualitatively similar after the po and iv doses. Marked differences in the protein binding of DP in human and dog plasma were found. In the papillary muscle, ventricular septum, and ventricles of one dog, the steady-state concentrations of DP and its less active mono-N-dealkylated metabolite were about twice those in plasma, whereas in the atria and tricuspid and mitral valves they were similar to those in plasma.

Administration, Oral↗