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D J Chapron

Publications and source records attributed to D J Chapron.

29 records · Page 2Linked to original sources
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↗
PubMed1980

Kinetic discrimination of three sulfamethazine acetylation phenotypes.

The relationship between sulfamethazine disposition kinetics and acetylator phenotype was studied in 19 healthy subjects. Various kinetic parameters for sulfamethazine and its N4-acetylated metabolite were determined after a dose of a rapidly absorbed oral solution. When plotted on a frequency distribution histogram, the results exhibited a well-defined trimodal pattern for acetylation clearance values and overall elimination or metabolic rate constants. These data were consistent with the well-recognized acetylation polymorphism for sulfamethazine, except that they clearly subdivided the previously acknowledged "fast" acetylator mode into intermediate and rapid acetylator groups. The apparent distribution volume and renal clearance for sulfamethazine and acetylsulfamethazine did not differ significantly among the 3 phenotypes. Of special interest was the observation that rapid acetylators initially produce much greater amounts of acetyl metabolite than intermediate acetylators. The potential clinical implications of identifying rapid and intermediate acetylators are discussed in view of evidence showing that acetyl metabolites may be pharmacologically active or function as intermediates in toxic metabolic pathways.

Acetylation↗
PubMed1979

Effect of calcium and antacids on phenytoin bioavailability.

The effects of bihourly administration of gluconate calcium and tow magnesium-aluminum-containing acids on the bioavailability of a single capsule dose of phenytoin sodium were determined in two normal volunteers. Neither the rate nor the extent of phenytoin absorption were altered by the treatments, in spite of indirect evidence from other studies that might suggest such an interaction. No interaction between calcium or magnesium and either unionized or anionic phenytoin could be demonstrated in vitro using solubility and spectral techniques.

Aluminum Hydroxide↗
PubMed1979

Apparent quinidine-induced digoxin toxicity after withdrawal of pentobarbital: a case of sequential drug interactions.

Accelerated quinidine metabolism was observed in a 94-year-old woman also receiving daily doses of digoxin and pentobarbital sodium. Discontinuation of pentobarbital produced a sharp increase in serum digoxin concentrations coupled with symptoms highly suggestive of digoxin toxicity. Associated with these findings was 3.8-fold increase in quinidine half-life. These data seemed consistent with an interaction between quinidine and digoxin that was precipitated by pentobarbital withdrawal.

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PubMed1978

Tetracycline absorption in elderly patients with achlorhydria.

Five elderly achlorhydric patients and five controls took 250 mg tetracycline as a capsule or as an oral solution. Venous blood samples drawn during the 12-hr period following administration and urine collected for 72 hr post-dosing were assayed fluorometrically for tetracycline. There were no differences between the two groups in either rate or extent of tetracycline absorption. The mean apparent first-order rate constant (ka) for absorption of drug from capsules was 0.58 +/- 0.17 hr-1 for patients and 0.65 +/- 0.21 hr-1 for controls. The mean extent of absorption for capsule dosage forms relative to an oral solution was 1.0 +/- 0.20 for patients and 1.0 +/- 0.24 for controls. Concurrent administration of 2 gm of sodium bicarbonate to 2 of the normal subjects resulted in no impairment of either the rate or extent of tetracycline absorption from capsules, suggesting that the effect of elevated gastric pH on tetracycline bioavailability may relate to formulation.

Achlorhydria↗
PubMed1978

Evidence for a trimodal pattern of acetylation of isoniazid in uremic subjects.

Isoniazid metabolic clearance values were calculated retrospectively and plotted on a frequency distribution histogram. A trimodal distribution pattern was observed. According to a two-allele codominant model, the mean clearance values of the slow and rapid acetylators closely predicted the mean clearance value for the intermediate acetylators. The potential clinical implications of identifying intermediate and rapid acetylators of isoniazid and its use in renal failure are discussed.

Acetylation↗
PubMedDate not supplied

Potential influence of body weight on the clearance of polymorphically acetylated drugs.

The acetylation clearance of sulfamethazine was found to be significantly dependent upon body weight in both intermediate and rapid acetylators. The correlation between acetylation clearance and body weight was stronger in the rapid acetylator. It is recommended that weight-corrected acetylation clearance values be used when constructing distribution histograms for phenotyping purposes. Within a phenotypic mode, body weight may be useful in providing initial estimates of dosing needs.

Acetylation↗
PubMedDate not supplied

Gastric retention of enteric-coated magnesium chloride tablets.

OBJECTIVE: To describe a patient with gastric retention of enteric-coated magnesium chloride tablets. Potential drug and disease etiologies accounting for failure to empty this dosage form are discussed. DESIGN: Single case report. CASE SUMMARY: A seriously ill patient with metastatic small-cell lung cancer accumulated 21 enteric-coated magnesium chloride tablets in his stomach during a four-day administration period. The patient had gastroscopic evidence of mild pylorospasm and suspected gastric motor dysfunction. The latter may have been the result of several factors including concurrent use of oxycodone, vagal dysfunction from chronic alcoholism and cisplatin-based chemotherapy, and possibly a paraneoplastic neuromuscular syndrome involving the gastrointestinal tract. CONCLUSIONS: Enteric-coated tablets are indigestible solids, often of considerable size. Strong antral contractions, associated with phase 3 of the interdigestive migrating myoelectric complex, are usually required to carry such dosage forms through a normal pyloric channel and into the duodenum. Seriously ill patients who may have gastric hypomotility or pyloric channel narrowing are probably not good candidates for therapy with large enteric-coated dosage forms.

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