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Biomedical subjects

A Karim

Publications and source records attributed to A Karim.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effects of misoprostol on the pharmacokinetics of indomethacin in human volunteers.

The effects of misoprostol (200 micrograms as a single dose or q.i.d. as a multiple dose) on the pharmacokinetics of indomethacin (100 mg single-dose administration or 50 mg t.i.d. multiple-dose administration) were studied in 16 healthy human volunteers under single-dose and steady-state conditions in a randomized, double-blind, placebo-controlled, balanced three-period study design. The overall absorption as shown by the values for area under the concentration curve of indomethacin was unaffected by concurrent administration of misoprostol. However, misoprostol did significantly enhance the steady-state maximum concentration of indomethacin by 32%. Thus misoprostol does not interfere with the absorption of indomethacin despite the known inhibitory effects of this protaglandin analog on acid secretion.

Administration, Oral↗
PubMed1992

Gastrografin-induced aspiration pneumonia: a lethal complication of computed tomography.

A 43-year-old man with dysphagia and a tendency to aspirate was found to have squamous cell carcinoma of the esophagus. Curative surgery was planned and preoperative computed tomography of the chest and abdomen was ordered. A ward nurse administered Gastrografin according to a "standing" order, 4 hours before the CT was to be done. The patient aspirated about 50 mL of Gastrografin, and went into cardiorespiratory arrest caused by pulmonary edema. He sustained severe brain damage and died. This is a first report of lethal aspiration of Gastrografin, given in preparation for CT. We advise alerting nurses who administer Gastrografin, especially to patients with dysphagia or impaired consciousness about the grave consequences that can result if the contrast agent is aspirated by the patient. We further advise that responsibility for using contrast agents in radiologic procedures be assumed by the radiologist and not by medical house staff.

Adult↗
PubMed1992

Biopharmaceutical profile of diclofenac-misoprostol combination tablet, Arthrotec.

Arthrotec, a combination tablet has been developed that contains 50 mg of diclofenac in an inner core and 200 micrograms of misoprostol in an outer mantle. Both diclofenac and misoprostol are extensively absorbed and their maximum plasma concentrations, but not total availability, are diminished when taken with food. Both drugs have elimination half-lives of less than 2 hours and do not accumulate in plasma after recommended doses. Pharmacokinetic and bioavailability studies of the combination product taken separately and together reveal a high between- and within-subject variability in plasma diclofenac levels, especially when the enteric-coated tablets were given after food; reliable values for peak plasma diclofenac concentration could not be ascertained. No pharmacokinetic interactions between diclofenac and misoprostol were apparent. The bioavailability of diclofenac and misoprostol from the combination tablet was similar to that seen when the two drugs are given separately.

Administration, Oral↗
PubMed1992

[The "HELLP" syndrome: a severe sign in toxemia. Three new cases].

Three women with hypertension, admitted for severe epigastric pain in the third trimester of pregnancy had a complete HS. All 3 women recovered spontaneously 3 days after delivery. All clinical and laboratory findings rapidly disappeared. A premature labour was a neonatal death at 26 weeks. The 2 other infants had delivered by caesarean section because the cardiotocogram showed signs of fetal hypoxemia.

Abortion, Therapeutic↗
PubMed1990

Metabolism and pharmacokinetics of nufenoxole in animals and humans: an example of stereospecific hydroxylation of an isoquinuclidine ring.

1. Nufenoxole, a novel antidiarrhoeal agent, was well absorbed in rat, monkey and human after oral administration. Systemic availability of nufenoxole was 85% in monkey and 102% in man. 2. The elimination rate was much faster in rat (t1/2 of 1.8 h) and monkey (t1/2 of 4.9 h) compared with human (t1/2 of 35.8 h). 3. After oral and i.v. 14C-nufenoxole, concentrations of 14C in human erythrocytes and saliva were approx. 3- and 4-fold lower, respectively, than plasma concentrations. 4. Nufenoxole was metabolized to metabolites hydroxylated on the methyl substituent and isoquinuclidine ring in rat and monkey. The isoquinuclidine ring hydroxylation, a major pathway in human, was stereospecific. 5. Following oral doses of 14C-nufenoxole the urinary excretion of radioactivity (about 8%) was less than the faecal excretion (66.6%) in rat, while urinary excretion was the major route of drug elimination (about 60%) in man. In monkey, urinary and faecal excretion were equally important.

Adult↗
PubMed1990

Pharmacokinetics of misoprostol in the elderly, in patients with renal failure and when coadministered with NSAID or antipyrine, propranolol or diazepam.

The pharmacokinetics of misoprostol were examined in the following contexts: in coadministration with the nonsteroidal antiinflammatory agents (NSAID) aspirin, diclofenac, ibuprofen, indomethacin and piroxicam; in coadministration with agents extensively metabolized by the liver--i.e., antipyrine, propranolol and diazepam; in healthy elderly subjects; and in patients with various degrees of renal failure. No clinically important interactions between misoprostol and NSAID were observed. Similarly, no metabolic interactions between misoprostol and antipyrine, propranolol or diazepam were noted. Pharmacokinetic variable values in elderly subjects did not differ in a clinically significant manner from those in younger subjects. Finally, although values for some pharmacokinetic variables--maximum concentration of misoprostol acid, area under the concentration-time curve and elimination half-life--were increased in patients with renal failure compared with controls, these alterations do not warrant changes in misoprostol dosage. These factors are particularly relevant to safety of misoprostol administration in elderly individuals, who not only consume more NSAID than young adults, but are also more likely to have intercurrent nonarthritic illness requiring additional medication and potentially modifying drug kinetics.

Adult↗
PubMed1989

Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites.

Metabolism of spironolactone in man is extensive and complex. For many years the dethioacetylated metabolite, canrenone, was assumed to be the major metabolite. However, recent studies using specific high performance liquid chromatography (HPLC) have demonstrated the presence of spironolactone and the sulfur-containing metabolites 7 alpha-thiomethylspirolactone (IV) and 6 beta-hydroxy-7 alpha-thiomethylspirolactone (V), in addition to canrenone, in the serum after a single oral dose of spironolactone. The importance of spironolactone and metabolites IV and V relative to canrenone at steady state remains unknown and was the subject of the present investigation. Twelve healthy males received 100 mg spironolactone, once daily, for 15 days. Repeated blood samples were taken on days 1, 8 and 15 for estimation of spironolactone and its metabolites. Peak serum levels [mean (SD)] of spironolactone, canrenone, and sulfur-containing metabolites IV and V were 72 (45), 155 (43), 359 (106) and 101 (26) ng/ml, respectively on day 1 and 80 (20), 181 (39), 391 (118) and 125 (24) ng/ml, respectively on day 15. The AUC (0-24) values of these compounds on day 15 were 231 (50), 2173 (312), 2804 (777) and 1727 (367) ng.hr/ml, respectively and the post-steady state elimination half-life (t1/2) values were 1.4 (0.5), 16.5 (6.3), 13.8 (6.4), and 15.0 (4.0) hours, respectively. It was concluded that unmetabolized spironolactone is present in the serum and that the sulfur-containing metabolite IV rather than canrenone is the major metabolite in serum following single or repeated doses of spironolactone.

Adolescent↗
PubMed1989

Effects of food and antacid on oral absorption of misoprostol, a synthetic prostaglandin E1 analog.

Misoprostol, a synthetic PGE1 analog with mucosal protective and antisecretory properties, is rapidly and essentially completely metabolized to its active metabolite, misoprostol acid. Relative to fasting conditions administration of misoprostol with antacid resulted in reduced bioavailability, as manifested by lower AUC(0-4) values from (mean +/- SD; n = 12) 417 +/- 135 to 349 +/- 108 pg.hr/ml (P less than 0.05), without significant changes in the rate of absorption (tmax = 14 +/- 8 [fasting] vs. 20 +/- 14 min [with antacid]). The observed Cmax values were also reduced (from 811 +/- 317 to 689 +/- 315 pg/ml), however, the difference was not statistically significant. Drug administration with a high-fat content meal resulted in a marked slowing in the absorption rate without a substantial decrease in the extent. Relative to fasting conditions food decreased misoprostol acid Cmax from 811 +/- 317 to 303 +/- 176 pg/ml (P less than 0.05) and increased tmax from 14 +/- 8 to 64 +/- 79 min (P less than 0.05): the AUC changes remained statistically insignificant from 417 +/- 135 to 373 +/- 111 pg.hr/ml. Administration of misoprostol with food could potentially decrease the incidence of systemic side effects by reducing the early high peak plasma concentrations of misoprostol acid.

Administration, Oral↗
PubMed1989

A scanning electron microscope study of human pulp fibroblasts in culture.

Human pulp tissue was obtained from the first lower right molar of a 24 year old male patient during oral surgery. The tooth was healthy with no evidence of carious lesions. 6 cultures were initiated by the explant method. The cells were isolated and carried through 8 passages. Samples from different passages were fixed, dehydrated, and prepared for scanning electron microscopic observations. Some cells had a smooth surface, while others showed microvillous projections from their surface. Both cell types were seen in the same culture. However, in the third passage all the cells were of the smooth surface type. The cells were interconnected by a system of fibrils that were related to their surface. These fibrils also appeared to anchor the cells to the surface of the coverslips on which they were growing. This study showed that more than one cell type apparently existed in human pulp fibroblasts culture. Whether these cell types have different functional properties, or whether they are different developmental stages of the same cell type in culture, remain to be determined.

Adult↗
PubMed1987

Theophylline absorption from sustained-release products: comparative steady-state bioavailability of once-daily Theo-Dur, Theo-24, and Uniphyl.

Theophylline absorption from three sustained-release formulations was evaluated in 18 healthy men. First, a 600-mg oral dose of aminophylline, a rapidly absorbed formulation, was studied to confirm that theophylline clearance was in the expected range (mean +/- SD, 0.710 +/- 0.096 mL/min/kg), t1/2 = 6.9 +/- 1.1 hr. Then each of the three sustained-release formulations was given at one hour before breakfast for eight days to achieve steady state. Multiple blood samples were drawn on days 7 and 8 over two complete dosing intervals. After a six-day drug-free period each subject was crossed over to the next product. At steady state, mean fluctuations of serum theophylline levels were more than 200% with Theo-Dur (Key Pharmaceuticals, Miami, FL), more than 150% with Uniphyl (Purdue-Frederick, Norwalk, CT), and about 75% with Theo-24 (Searle Laboratories, Chicago, IL). Theophylline Cmax levels averaged 16.5 micrograms/mL after 900 mg Theo-Dur, with 8% exceeding 20 micrograms/mL. Despite these high peak levels, nearly half of the Cmin levels were below 5 micrograms/mL. Uniphyl administration resulted in three-fourths of trough levels to be at 5 micrograms/mL or lower. Peak levels from 800-mg daily doses of Uniphyl were also low, with 42% never reaching 10 micrograms/mL. With Theo-24 only 17% of trough levels were below 5 micrograms/mL, as compared to 47% with Theo-Dur and 72% with Uniphyl. The three products differed in the areas under the serum concentration-time curves (AUC), which reflect bioavailability. Theo-Dur AUC was nearly equivalent to that of rapidly absorbed aminophylline (when adjusted for dosage).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Antiulcer prostaglandin misoprostol: single and multiple dose pharmacokinetic profile.

Low misoprostol dose (microgram range), extremely low plasma levels (pg range) of misoprostol acid, and the necessity of using a complex, time consuming, and labor intensive RIA method of analysis make it technically difficult to study the pharmacokinetic profile of misoprostol in man. The clinical relevance of the misoprostol pharmacokinetic data should be interpreted with care in view of the combined local and systemic effects of the drug. The studies presented in the present review indicate: Extensive metabolism of misoprostol occurs during and/or prior to gastrointestinal absorption. Several metabolites are formed and no unchanged drug is detected in the plasma or urine. The biologically active metabolite in the plasma is misoprostol acid (SC-30695), a de-esterified derivative of misoprostol. Absorption of misoprostol and/or misoprostol acid is extremely rapid resulting in peak plasma levels of misoprostol acid in less than 15 minutes. Absorption probably occurs in the stomach. The elimination half-life of misoprostol acid is short (less than 30 minutes). No accumulation of misoprostol acid occurs in plasma following a 400 microgram q12h dosing regimen of misoprostol.

Adult↗
PubMed1986

Effects of food on the bioavailability of theophylline from controlled-release products in adults.

A variety of formulation-dependent food-induced absorption changes ("food effect") occur with controlled-release formulations of theophylline. These changes are found in formulations with either pH-dependent or pH-independent in vitro dissolution characteristics. They include decreases in the rate or extent, increases in the rate and extent, and more erratic or variable theophylline absorption. In evaluating food effects from a test formulation, it is essential to standardize the meal composition (fat content) and dosing time relative to meal intake. For those formulations that exhibit pronounced food effect, drug dosing relative to meal intake should be made part of product labeling to assure consistent absorption.

Adult↗
PubMed1985

Food-induced changes in theophylline absorption from controlled-release formulations. Part I. Substantial increased and decreased absorption with Uniphyl tablets and Theo-Dur Sprinkle.

Food-induced changes in absorption from two controlled-release formulations of theophylline (Uniphyl tablets [Purdue Frederick Co.] and Theo-Dur Sprinkle [Key Pharmaceuticals, Inc.]) were studied in healthy male nonsmokers. Although the two forms exhibited a theophylline in vitro dissolution rate that was independent of changes in pH from 1 to 8, they showed substantial but opposite food-induced absorption changes. In a 12-subject, three-way, single-dose, randomized, crossover study the bioavailability of theophylline relative to immediate-release aminophylline tablets increased from 53% +/- 23% (means +/- SD) to 96% +/- 46% when Uniphyl (two 400 mg tablets) was taken under fasting and nonfasting (high fat content meal) conditions, respectively. On the other hand, in a separate six-subject, two-way, randomized, crossover study, food reduced the bioavailability of theophylline from Theo-Dur Sprinkle: Theophylline bioavailability in the nonfasting state was only 53% +/- 9% that in the fasting state.

Absorption↗