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E J Antal

Publications and source records attributed to E J Antal.

45 records · Page 3Linked to original sources
PubMed1983

Influence of route of administration on the pharmacokinetics of methylprednisolone.

This study was conducted to evaluate the influence of route of administration upon the bioavailability and pharmacokinetics of methylprednisolone sodium succinate. Fourteen healthy adult male volunteers received 40 mg doses of methylprednisolone as the following treatments after an overnight fast in a 4-way crossover design: (a) as a 1 ml i.v. bolus; (b) as a 1 ml i.m. injection; (c) administered as an oral solution; and (d) as 5 X 8 mg oral tablets. Both the ester and free methylprednisolone were determined in plasma and urine. Study results indicate that the ester is rapidly and extensively converted to free methylprednisolone after all routes. The extent of methylprednisolone absorption was equivalent after i.v. and i.m. administration. Both orally administered treatments resulted in a lower extent of absorption attributed to a first-pass effect. Although a slightly lower extent of absorption was demonstrated following the oral administration of the methylprednisolone sodium succinate solution relative to the methylprednisolone oral tablets, this average difference of 9% would probably be of minimal therapeutic importance.

Absorption↗
PubMed1983

Ibuprofen and acetaminophen kinetics when taken concurrently.

We evaluated kinetics of ibuprofen and acetaminophen taken concurrently by 20 healthy adults in a randomized crossover design. Steady-state blood levels of ibuprofen and acetaminophen were measured by gas-liquid chromatography and HPLC. There were no significant differences in any of the ibuprofen serum concentrations, but there were differences in acetaminophen serum concentrations in 5 of 19 sampling times. When bioavailability and kinetic parameters for both drugs were compared, there were no significant differences. Our data demonstrate that steady-state kinetics of ibuprofen and acetaminophen are not changed when taken concurrently.

Absorption↗
PubMed1983

The bioavailability of an orally administered medroxyprogesterone acetate suspension.

The relative bioavailability of an orally administered aqueous suspension of medroxyprogesterone acetate (MPA) intended for intramuscular injection (Depo-Provera) was determined in relation to orally administered tablets. Serum levels of MPA were determined by radioimmunoassay following the administration of 400-mg doses to 19 adult male volunteers in a crossover design after an overnight fast. The two treatments were judged bioequivalent based upon a comparison of the resultant MPA serum levels and the derived bioavailability parameters. Hence, the intramuscular suspension administered orally offers an alternative means of achieving optimal serum levels of MPA in patients requiring high dose therapy.

Administration, Oral↗
PubMed1982

The effect of food on the bioavailability and pharmacodynamics of tolbutamide in diabetic patients.

The effect of food on the rate and extent of absorption of tolbutamide in diabetic patients was studied by varying the time of drug administration in relation to the ingestion of a standard meal. Serum levels of tolbutamide, insulin and glucose and related bioavailability parameters were compared following the administration of a single dose of tolbutamide 0.5 g to diabetic patients 30 min prior to and immediately before a standardized meal. A placebo dosage form was also administered to determine baseline glucose and insulin response to the meal. The 700 calorie standard meal was composed of 41% carbohydrate, 18% protein, and 41% fat. Administration of the drug with the meal resulted in a 6% (statistically significant) decrease in the extent of absorption, as determined by measurement of the area under the tolbutamide serum level-time curve from zero to infinity. Serum levels of tolbutamide were also significantly higher 0.5 h after drug administration when the drug was taken with the meal. Except for these two minor effects, no other differences between the drug treatments were observed in any other parameters of tolbutamide absorption or in the postprandial glucose and insulin serum levels. Therefore, the small differences found were judged to be clinically meaningless. These findings demonstrate that administration of tolbutamide 0.5 g tablets 30 min prior to or with a standard meal results in equivalent therapeutic actions.

Adult↗
PubMed1982

Estimating steady state desipramine levels in noninstitutionalized elderly patients using single dose disposition parameters.

Clearances calculated from single oral dose data have been utilized to predict steady state levels of desipramine in 12 noninstitutionalized depressed elderly patients. Observed steady state plasma levels correlated very well (r = 0.967, p less than 0.0005) with those predicted from single dose clearances, but not with plasma levels obtained 20 hours after a single oral dose (r = 0.24, p greater than 0.2). The mean half-life of desipramine (20.9 hours) in this group of elderly (mean age, 72 years) was considerably less than values of "apparent disappearance" half-life previously reported for elderly patients receiving imipramine. The single dose clearance technique yielded a precise criterion for quantitating early compliance with and adjusting drug dosing regimens.

Aged↗
PubMed1981

Theophylline pharmacokinetics in advanced age.

1 Theophylline kinetics following a single oral dose were characterized and compared in non-institutionalized ambulatory elderly and young gender-matched control subjects. Study design stressed stringent, yet realistic, control of several external factors known to influence theophylline metabolism. 2 Plasma levels of total drug were significantly higher in the elderly only at early sampling times (0.5 and 1 h) and at 36 h, while unbound theophylline levels were significantly higher (P less than 0.05) at all sampling times resulting in a 45% greater AUC for unbound drug. 3 While no significant differences in volume of distribution (Vd) or overall plasma clearance were observed when calculations were based on total plasma theophylline, a 37% reduction in Vd (P less than 0.005) and a 30% reduction in overall plasma clearance (P less than 0.02) in the elderly became apparent when plasma protein binding was taken into account. 4 When urinary excretion patterns were compared, the elderly were found to have excreted a significantly higher fraction of the recovered dose as 1-methyluric acid (P less than 0.01) and a lower fraction as unchanged theophylline (P less than 0.02). A 47% reduction in the renal clearance of unbound theophylline (P less than 0.005) was also observed in the elderly. 5 Results were consistent with less viable metabolism and renal excretion pathways for theophylline elimination in the elderly and serve to reemphasize the importance of including an assessment of plasma protein binding in studies of drug disposition in the elderly.

Adult↗
PubMed1975

Bioequivalency of doxycycline products.

The bioavailability of three different brands and three different dosage forms of doxycycline was studied in normal subjects. Single doses, equivalent to 200 mg of doxycycline, were administered to six subjects in a crossover design as the innovator's intravenous solution given orally (Treatment A), the innovator's capsule product (Treatment B), a noninnovator's capsule product (Treatment C), the innovator's oral suspension product (Treatment D), and a second noninnovator's capsule product (Treatment E). All dosage forms contained doxycycline as the hyclate, except the suspension which contained the nonhyclate form. Serum levels were determined periodically over 48 hr, and cumulative urinary excretion was measured concurrently over a 120-hr collection period. No statistically significant differences were observed in any in vivo indicator of bioequivalence when the three capsule products were compared. Consequently, they were judged to be bioequivalent. When these capsule products were compared to the oral solution, no statistically significant differences were observed. However, when the capsules and the suspension were compared, statistically significant differences were found in the rate of absorption. In vitro dissolution tests were also conducted on the three brands of capsules, and times required to achieve 50% dissolution showed rank-order correlation with corresponding absorption rate constants.

Adult↗
PubMedDate not supplied

Effect of injection volume on the bioavailability of sterile medroxyprogesterone acetate suspension.

The influence of injection volume on the absorption and bioavailability of medroxyprogesterone acetate (MPA) was studied. A single i.m. injection of MPA 400 mg was administered to 24 healthy men; 12 of the subjects received 4 ml of a 100 mg/ml suspension of the drug, and the other 12 subjects were given 1 ml of a 400 mg/ml suspension. Blood samples for MPA determinations were collected periodically during a 202-day period after drug administration. Mean steady-state serum concentrations of MPA were simulated from single-dose data to reflect those achieved after standard dosage regimens. Values for area under the serum concentration-time curve and time required to reach peak serum concentrations were compared between subjects receiving different injection volumes of MPA. Mean peak serum concentration were significantly higher and occurred significantly sooner in subjects receiving the 4-ml injection of MPA than in those given the 1-ml injection. No significant differences in areas under the serum concentration-time curve were noted in subjects receiving different injection volumes. The rate but not the extent of absorption of injectable MPA suspension is enhanced by increasing the injection volume of equivalent doses from 1 ml to 4 ml.

Adult↗