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Biomedical subjects

F Jamali

Publications and source records attributed to F Jamali.

At least 127 records · Page 7Linked to original sources
PubMed1986

Direct injection high-performance liquid chromatography of tetrabenazine and its metabolite in plasma of humans and rats.

A convenient, selective, and sensitive reversed-phase HPLC assay was developed to measure concentrations of the dopamine-depleting agent, tetrabenazine (1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo(a)quinoli zin-2-one) and its dihydro metabolite in the plasma of patients with tardive dyskinesia receiving therapeutic doses of the drug and in the plasma of rats. The method involves plasma protein precipitation, oxidation of the compounds with mercuric acetate at 110 degrees C for 1 h, addition of internal standard, and injection into the instrument. Fluorescence detection was utilized at excitation and emission wavelengths of 265 and 418 nm, respectively. The peaks from the drug, its metabolite, and at least three other substances were best resolved at 60 degrees C using a mobile phase of water:acetonitrile:acetic acid:triethylamine (65:33:2:0.15) at a flow rate of 0.6 mL/min; the 4.6 mm X 10 cm column contained 5 micron of octadecylsilane packing. To assess the applicability of the assay, the drug was administered intravenously to rats, and plasma concentrations were determined before (by UV-HPLC) and after (by fluorescence-HPLC) the oxidative procedure. In addition, the MS spectra of tetrabenazine and the dihydro metabolite, isolated from biological samples, were identical to those of authentic samples. Excellent linearity was observed between the peak area ratios and concentrations over the ranges 0.5-200 and 2-1000 ng/mL of the drug and the metabolite, respectively. Minimum quantifiable concentrations of the drug and its metabolite were 0.5 and 2.0 ng/mL, respectively. The sensitivity was found to be adequate for pharmacokinetic studies of tetrabenazine in humans and rats.

Animals↗
PubMed1985

Pharmacokinetics of tiaprofenic acid in healthy and arthritic subjects.

Disposition kinetics of nonsteroidal, anti-inflammatory tiaprofenic acid (1) and its metabolites were studied in healthy subjects and arthritic patients under treatment with 200 mg of the drug three times daily. The concentration of the drug and its metabolites were measured using a sensitive and specific HPLC method. The pharmacokinetics of tiaprofenic acid in arthritic patients seems to be similar to those in healthy subjects. The drug is rapidly absorbed, extensively bound to plasma proteins and, upon repeated administration, is accumulated in the body only to a limited extent. While only unchanged drug was found in plasma, a negligible amount of the unchanged drug was recovered from urine. The major pathway of drug elimination seems to be through conjugation. The reduced and oxidized metabolites of 1, 2 and 3, respectively also are found in urine as conjugates. The conjugates are, however, relatively unstable and are readily hydrolyzed to their parent compounds upon storage or addition of alkali. As elimination of the drug is dependent upon urinary excretion of the conjugates, it may be influenced by reduced renal function or the presence of other drugs.

Adult↗
PubMed1985

Lack of pharmacokinetic interaction between cimetidine and pirenzepine.

The oral administration of pirenzepine (PRZ), an antimuscarinic agent, has a variable effect on gastric acid secretion in patients with duodenal ulcer, and it seems to potentiate cimetidine-induced inhibition of secretion. The possibility of a pharmacokinetic interaction between these drugs was examined in eight patients who received cimetidine and PRZ alone and in combination in a crossover fashion. Cimetidine, 600 mg b.i.d., PRZ, 50 mg b.i.d., or combination therapy were each given for 1 week before the study. Serum samples were serially drawn during each dosing interval for determination of cimetidine and PRZ concentrations by HPLC and RIA, respectively. Cimetidine given alone or with PRZ exhibited diurnal variation, as the peak serum concentration was lower after the nighttime dose than after the morning dose. PRZ showed intersubject variation. However, each drug failed to alter the pharmacokinetic indices of the other. The times to attain the peak serum concentration were not significantly different for cimetidine alone or with PRZ, arguing against an effect of PRZ on gastric motility in the doses we used. The greater and prolonged acid inhibition with the combination of cimetidine and PRZ, therefore, may stem from a synergistic action of both drugs on receptor sites on gastric parietal cells.

Administration, Oral↗
PubMed1984

High-performance liquid chromatographic analysis of tiaprofenic acid and its metabolites in plasma and urine by direct injection.

A rapid, convenient, sensitive and selective reversed-phase high-performance liquid chromatographic method was developed to measure tiaprofenic acid, its reduced and oxidized metabolites and their conjugates in biological fluids. The method involved direct injections of plasma and urine samples into the chromatograph before and after alkaline hydrolysis of the conjugates. Concentrations as low as 0.5 micrograms/ml of the drug in plasma and urine were quantifiable. The method was suitable for analysis of tiaprofenic acid and its metabolites in biological fluids after administration of therapeutic doses. Several other non-steroidal anti-inflammatory drugs which were applied to the system did not interfere with the assay.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1984

Low-dose methotrexate kinetics in arthritis.

Twelve patients with either rheumatoid or psoriatic arthritis were injected with a 10-mg bolus dose of methotrexate (MTX) either intramuscularly (n = 6) or intravenously (n = 6) and the MTX concentration in their sera was determined by radioimmunoassay. MTX concentration--time data fitted triexponential equations. Doses injected intramuscularly were rapidly and completely absorbed. There were no significant intergroup differences in drug mean t 1/2, volume of distribution, and total body clearance. In nine patients serum MTX concentrations remained above the suggested critical level of 0.01 mumol throughout the 24-hr study irrespective of the route of administration, but MTX did not cumulate in the serum. We conclude that the behavior of low doses of MTX in patients with arthritis closely resembles the pattern in patients receiving intermediate and high doses for the treatment of neoplasia.

Absorption↗
PubMed1984

Comparative effects of two cimetidine regimens on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer.

The effect of 600 mg of cimetidine given twice daily on 24-hour intragastric hydrogen ion (H+) concentration was compared with that of the standard regimen of 300 mg of cimetidine given four times daily in six patients with asymptomatic duodenal ulcer. According to the double-blind, Latin-square, repeated-measures design, all subjects followed each cimetidine regimen and a placebo regimen for one week. Acid secretion studies and determinations of drug and gastrin levels in the blood were carried out on the last day of each treatment week. Although 600 mg of cimetidine BID suppressed H+ after breakfast and during the night, compared with placebo treatment (P less than 0.01), the 300-mg QID regimen suppressed H+ only after breakfast and supper (P less than 0.05). A higher percentage of pH readings greater than or equal to 3.0 were obtained with 600 mg of cimetidine BID than with 300 mg of cimetidine QID during the night (P less than 0.05); compared with percentages when placebo was taken, the percentages of pH readings greater than or equal to 3.0 were greater both overnight and during a 24-hour period only when 600 mg of cimetidine was given BID (P less than 0.01). The observed difference in intragastric H+ suppression after each regimen could not be explained by variations in serum concentrations of cimetidine or serum concentrations of gastrin. Despite similar peaks of serum cimetidine after evening doses of 300 or 600 mg of cimetidine, nocturnal intragastric acidity was lower in subjects given 600 mg BID. Further, H+ levels after lunch were similar in both cimetidine-treated groups, despite markedly higher serum cimetidine concentrations in patients receiving 600 mg BID. Pharmacokinetic studies showed equivalent elimination half-times and 24-hour areas under the curve of serum cimetidine concentration in patients on the two cimetidine regimens. Postprandial integrated gastrin responses were of similar magnitude in patients on either cimetidine regimen. There was no significant difference in mean serum gastrin concentrations during the night in placebo-treated and cimetidine-treated patients. Only a weak correlation was observed between H+ and serum gastrin concentration. Although a fluctuation of the H+:gastrin ratio occurred after each meal in all groups, the ratio was suppressed by both dosages of cimetidine. The findings suggest that a regimen of 600 mg of cimetidine BID is superior to the standard regimen of 300 mg QID in suppressing intragastric acidity in patients with asymptomatic duodenal ulcer.

Adult↗
PubMed1984

Effect of combination of antacid and cimetidine on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer.

UNLABELLED: By means of a Latin square design, the effect of antacid alone and in combination with cimetidine on a 24-hour intragastric hydrogen ion (H+) activity and serum gastrin profiles was studied in eight patients with duodenal ulcer. Antacid given seven times a day (one and three hours after meals and at bedtime) combined with 600 mg BID of cimetidine (C + A7) achieved greater suppression of H+ after breakfast, overnight, and over the 24-hour period than did antacid alone seven times daily (A7). Antacid given four times a day (one and three hours after lunch and after supper) combined with cimetidine BID (C + A4) maintained the neutralizing capacity during this time, but was less effective than the C + A7 regimen. However, C + A4 produced more suppression of nocturnal H+ than did A7. A higher percentage of the readings at or above pH 4.0 were obtained with C + A7 than with A7 or C + A4. A greater postprandial integrated gastrin response was obtained with all active treatments as compared with a placebo regimen. The mean peak cimetidine concentration (Cmax) was higher but the time to peak (Tmax) was shorter after the morning than after the evening dose. The area under the cimetidine concentration-time curve and the Cmax and Tmax values after the morning and evening doses of cimetidine were not affected by the coadministration of antacid. IN CONCLUSION: (1) combination therapy of cimetidine plus antacid is more effective than antacid alone in the reduction of intragastric H+; (2) antacid alone fails to suppress the overnight intragastric acidity; and (3) antacid given concurrently with cimetidine does not interfere with pharmacokinetic determinants of plasma cimetidine concentration.

Adult↗
PubMed1983

High-performance liquid chromatography of dipyrone and its active metabolite in biological fluids.

New high-performance liquid chromatography methods were developed to measure dipyrone and its active metabolite 4-monomethylaminoantipyrine (MAA) in biological fluids. While no detectable level of the unchanged dipyrone was found in plasma of four subjects taking 1000-mg oral doses of the drug, values ranging from 1.25 to 14.99 micrograms/ml of MAA were observed. Twenty-four hour urinary excretion of MAA varied from 9.56 to 21.21 mg. Concentrations as low as 0.25 micrograms/ml of MAA can be measured with acceptable coefficients of variation. The method, therefore, is suitable for microquantification of MAA in biological fluid which enables convenient and rapid assessment of the drug disposition in body.

Adult↗
PubMed1980

Clinical significance of total serum IgE determination in screening of Iranian Russian thistle pollen hypersensitive individuals.

Total serum IgE concentrations of normal and Russian thistle (Salsola pestifer) pollen hypersensitive individuals were determined in an Iranian population, using the solid phase radioimmunoassay technique. The mean values were 963.7 and 885.3 ng/ml, respectively, which are much higher than normal values given for non-Iranian populations. In addition, no significant differences were found between observed values (P = 0.1) for normal and allergic individuals. The effect of common parasitic infestation in the Iranian population in causing high serum IgE levels is discussed.

Adolescent↗
PubMed1978

Griseofulvin---phenobarbital interaction: a formulation-dependent phenomenon.

The reported interaction of griseofulvin with phenobarbital was studied in the rat following oral administration of different dosage forms. A single oral dose of 15 mg of phenobarbital/kg 24 hr prior to the oral administration of a suspension of 100 mg og griseofulvin/kg in 0.5% polysorbate 80 significantly reduced plasma griseofulvin levels. An increase in the concentration of polysorbate 80 to 2% reduced the extent of the interaction from 50 to 32%. Phenobarbital did not influence plasma griseofulvin levels when griseofulvin was given in either 70% polyethylene glycol 300 (suspensions of 20 or 100 mg/kg) or 100% polyethylene glycol 600 (solution of 50 mg/kg). It is concluded that the observed interaction is formulation dependent and is a result of diminished dissolution and, consequently, reduced absorption of griseofulvin.

Animals↗
PubMedDate not supplied

Steady-state pharmacokinetics of metronidazole in Crohn's disease.

The pharmacokinetics of metronidazole (MTZ) were studied in six Crohn's disease patients after multiple oral daily doses of 250, 500, 750, and 1000 mg day-1. Pharmacokinetic indices were found to be independent of the dose administered. The half-life, volume of distribution and oral clearance of metronidazole were 9.5 +/- 2.1 h, 0.732 +/- 0.094 l kg-1 and 0.921 +/- 0.175 (ml min-1) kg-1 (mean +/- SD), respectively. A strong linear correlation (r = 0.95) was found between the volume of distribution of MTZ and the patients' total body weight. The percentage of dose of metronidazole excreted in urine as the intact drug and metabolites as well as glucuronic acid conjugates ranged from 34.7 +/- 7.4 to 58.9 +/- 5.2. Both plasma and urine data exhibited very large inter-patient variations. However, intra-patient variations were negligible. Strong positive linear correlations were observed between the dose and the areas under the plasma concentration versus time curves, peak plasma concentrations as well as cumulative urinary excretion of the drug and its metabolites. It is concluded that in Crohn's disease, the pharmacokinetics of MTZ and its metabolites are linear and that the drug concentrations are dependent on the total body weight.

Adult↗
PubMedDate not supplied

Comparative bioavailability of two flurbiprofen products: stereospecific versus conventional approach.

In this randomized, crossover study comparing the bioavailability of a film-coated (Ansaid) with a sugar-coated (Froben) 100 mg tablets of racemic flurbiprofen in 23 healthy young men, no significant differences were found for Cmax, tmax or AUC, using a nonstereoisomeric assay for flurbiprofen. Minor differences in the appearance of flurbiprofen in serum during the first 30-min post-dosing period were noted, with Ansaid appearing earlier than Froben. These differences likely reflect dissolution rate dissimilarity between the two products. Stereospecific determinations demonstrate a small (7.8 per cent) but significant difference in AUC of the active S-configuration (Froben greater than Ansaid). No significant differences between Ansaid and Froben were found for tmax or Cmax for the S-flurbiprofen. In bioequivalency studies of chiral drugs, stereospecific approaches provide a more accurate assessment of products.

Adolescent↗
PubMedDate not supplied

Interaction of metronidazole with phenobarbital, cimetidine, prednisone, and sulfasalazine in Crohn's disease.

The influence of prednisone(PR), sulfasalazine(SZ), cimetidine(CM), and phenobarbital(PB) on the pharmacokinetics of metronidazole was investigated in six Crohn's patients. Metronidazole was first administered alone (250 mg bid, po) and then with prednisone (10 mg bid, po), sulfasalazine (1 g bid, po), cimetidine (600 mg bid) or phenobarbital (60 mg bid, po). Each regimen was followed for 6 days and sampling of blood and urine was carried out on the 7th day after the first dose of each regimen. Plasma and urine samples were analysed for the drug and its two principal metabolites, hydroxymetronidazole and metronidazole-1-acetic acid, by HPLC. When given alone, metronidazole had a mean volume of distribution of 0.667 +/- 0.15 lkg-1, a half-life of 9.7 +/- 3.1 h and an oral clearance of 0.852 +/- 0.23 (ml-1 min) kg-1. The disposition kinetics of metronidazole and its metabolites was not altered by CM and SZ. Induction of metabolism of metronidazole by PR was made manifest in significant increases in oral clearance of the former and urinary excretion of the hydroxy metabolite, and significant decrease in AUC of the parent compound. PB also induced the metabolism of metronidazole. This induction was reflected in significant increases in the oral clearance of metronidazole and AUC of the hydroxy metabolite as well as significant decreases in AUC, half-life, and urinary excretion of the parent drug.

Chromatography, High Pressure Liquid↗