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Biomedical subjects

B H Dvorchik

Publications and source records attributed to B H Dvorchik.

At least 37 records · Page 2Linked to original sources
PubMed1978

Studies on theobromine disposition in normal subjects. Alterations induced by dietary abstention from or exposure to methylxanthines.

Normal male volunteers on xanthine-restricted diets had a plasma theobromine (TB) half-life (t1/2) of 6.1 +/- 0.7 hr (mean +/- SEM), a TB metabolic clearance rate (MCR) of 113.8 +/- 6.8 ml/min (mean +/- SEM), and an apparent volume of distribution (aVd) of 59.9 +/- 7.8 L (mean +/- SEM) after a single oral dose of 6 mg/kg of TB. A two-week period of dietary abstention from methylxanthines shortened the mean plasma TB t1/2 by 33% and increased the mean MCR of TB by 59%, no change occurred in mean aVd of TB. In another experiment, normal male volunteers received the same oral dose of TB for each of five consecutive days. The mean plasma TB t1/2 measured immediately after the last TB dose was prolonged by almost two-thirds, while the mean aVd increased 23%. Although the mean plasma TB t1/2 measured four days after this last TB dose was the same as that measured after a single oral dose, the mean MCR of TB increased by 34%, but this change was balanced by increased mean aVd of 35%. These results suggest that immediately after five daily doses of TB, an impairment of TB clearance occurs that is reversible by four days of dietary abstention from methylxanthines.

Adult↗
PubMed1977

Gas chromatographic determination of cocaine in whole blood and plasma using a nitrogen-sensitive flame ionization detector.

A procedure is described for the determination of as little as 20 ng of cocaine from 1 ml of whole blood or plasma. Methods are also given for the storage of whole blood or plasma containing cocaine as well as for whole blood or plasma extracts. Blood levels in patients receiving intranasal cocaine for topical anesthesia while undergoing rhinoplasty are also presented.

Chromatography, Gas↗
PubMed1976

Pharmacokinetic interpretation of data gathered during therapeutic drug monitoring.

We review some pharmacokinetic principles that can facilitate interpretation of data obtained during therapeutic drug monitoring: the one- and two-compartment models, volume of drug distribution, drug clearance, organ clearance, bioavailability, first-pass effect, chronic or repetitive dosing, and use of urine and saliva to measure drug clearance and drug binding to plasma proteins, respectively. We also describe use of saliva to estimate rapidly, conveniently, and noninvasively the concentration of the free, pharmacologically active form of the drug as well as the fraction of drug bound to plasma protein.

Administration, Oral↗
PubMed1976

Antenatal sex determination in Macaca arctoides.

Transabdominal amniocentesis was performed on 11 Macaca arctoides, between the 10th and 20th weeks of gestation, for the purpose of antenatal sex determination. The technique employing Y-chromatin fluorescence was unsuccessful in predicting sex, but the sexes were differentiated with complete accuracy by examining amniotic cells stained by a modified Papanicolaou technique. Of the cells from male fetuses, fewer than 10% contained X-chromatin (Barr bodies); of those from females, more than 45% contained X-chromatin.

Amniocentesis↗
PubMed1975

Gas chromatographic method for the microdetermination of barbiturates in blood using a nitrogen-selective flame ionization detector.

A rapid, quantitative gas-liquid chromatographic method for the simultaneous determination of as little as 10 ng of unmodified barbital, pentobarbital, secobarbital, and hexobarbital from whole blood is described. The method involves one extraction from whole blood into chloroform with subsequent injection into a gas chromatograph equipped with a nitrogen-sensitive flame ionization detector. This method has the advantages of small sample size high specificity, sensitivity, and rapidity.

Barbiturates↗
PubMed1975

Ultrastructure of the developing fetal hepatocyte of Macaca arctoides: a proposed model for studies of fetal drug metabolism.

The ultrastructure of the hepatocyte of the fetal stumptail monkey was examined with the aim of defining a possible model for studies of fetal drug metabolism. Hepatocytes from fetuses of 80 and 160 days gestation, as well as from one animal one week of postnatal age, were examined and compared to human fetal hepatocytes at 12 and 16 weeks gestation. Marked variation was observed in the amount of lipid and the distribution of organelles within the cytoplasm of the hepatocyte in the monkey population. These differences were attributed to genetic variation. Two changes were seen which correlated with developmental age. The amount of hemopoietic tissue decreased and the amount of smooth endoplasmic reticulum increased as the animal matured. The problems of genetic variation and the relative number of hepatocytes at different stages of development were discussed relative to the use of this animal as a model for fetal drug metabolism studies. Attention to both of these problems is considered necessary for the interpretation of biochemical data in future studies.

Animals↗
PubMed1975

Studies on the disposition of antipyrine, aminopyrine, and phenacetin using plasma, saliva, and urine.

In normal male subjects, the half-lives of antipyrine, aminopyrine, or phenacetin were not significantly different from the half-lives of each drug in saliva. Apparent volumes of distribution (aVd) in plasma and saliva differed by the extent to which each drug has been reported to bind to plasma proteins. Thus, the aVd of antipyrine in plasma and saliva was similar; there were significant differences in aVd for aminopyrine; even greater differences were observed for penacetin. The expression (see article) equals the fraction of the drug bound to plasma proteins. Rates of appearance in the urine of metabolites of antipyrine and aminopyrine were measured. General equations were used to show the relationship between half-life for elimination of the parent drug from the body and rate of excretion of metabolites. There were significant correlations between the half-life for elimination of antipyrine from the body and the half-life for production of 4-OH antipyrine (r equal 0.90), as well as between the plasma half-life of aminopyrine and the half-life of 4-aminoantipyrine (r equal 0.95). No significant correlation was observed in the same individual between the plasma half-lives of antipyrine and phenacetin (r equal 0.05, p greater than 0.05), of aminopyrine and phenacetin (r equal 0.11, p greater than 0.05), or of antipyrine and aminopyrine (r equal 0.50, p greater than 0.05).

Acetylation↗
PubMed1971

Does DDT inhibit carbonic anhydrase?

At a concentration of 50 to 100 micrograms per milliliter, p,p'-DDT (and p,p'-DDE) did not inhibit the rate of hydration or dehydration of carbon dioxide by carbonic anhydrase. At concentrations greater than 500 micrograms per milliliter, partial inhibition of the rate of dehydration of carbonic acid was observed, but this involved precipitation of drug in the reaction vessel. This degree of inhibition suggests that DDT may not inhibit carbonic anhydrase effectively at the usual concentrations found in tissue after exposure of organisms to DDT in the environment.

Carbonic Anhydrase Inhibitors↗
PubMedDate not supplied

Plasma protein binding of bepridil.

The binding of the calcium-channel blocking agent, bepridil HCl (Vascor), to plasma proteins was investigated using radiolabeled bepridil and equilibrium dialysis. Greater than 99.7% of added bepridil-14C was found to freshly collected human plasma. The binding was characterized by a saturable high-affinity site (KD = 32 ng/mL = 87 nM) on alpha1-acid glycoprotein (AAG) or on an AAG-human serum albumin complex and lower affinity binding sites on albumin and other plasma macromolecules. Bepridil that is not bound to plasma proteins is extensively distributed into erythrocytes as evidenced by a red blood cell to free drug distribution coefficient of 71 +/- 7. Despite this high value, the blood to plasma ratio of bepridil averaged only 0.67 in humans, indicating that most of the circulating drug is bound to plasma proteins. Bepridil protein binding was not affected by additions of nonesterified fatty acids. Free fractions of bepridil were enhanced by addition of verapamil, nifedipine, diltiazem, disopyramide, and warfarin but only at concentrations above those achieved clinically. Bepridil was also displaced by the plasticizer, tris-(2-butoxyethyl)phosphate. Plasma obtained from a small number of angina patients prior to bepridil administration showed no differences in ability to bind bepridil compared with plasma obtained from healthy subjects.

Angina Pectoris↗
PubMedDate not supplied

Drug biotransformation in microsomes from the fetal stumptailed macaque, Macaca arctoides: hepatic N-demethylation.

The kinetics of the N-demethylation of benzphetamine, ethylmorphine, meperidine, and methadone have been studied in microsomes isolated from livers of the fetal stumptailed macaque (Macaca arctoides) during the last third of gestation. The apparent KM for each substrate did not change during this time period. Values were similar to those from livers of adult African green monkeys. The Vmax for each substrate, when expressed per mg of microsomal protein, did not change during the last third of gestation. N-demethylase activity (Vmax) per g of liver increased during the last third of gestation, as did the content of microsomal protein, cytochrome P-450 concentration, and liver weight. The amount of cytochrome P-450 per g of liver was greater in whole homogenates of the left physiological lobe than in those of the right physiological lobe of fetal liver obtained near term; no differences occurred in whole homogenates of the separate lobes of adult liver. This observation suggests that a differential capacity for drug (and possibly steroid) metabolism may exist between the two physiological lobes of fetal liver.

Aging↗
PubMedDate not supplied

On the antipyrine test in laboratory animals. Studies in the dog and monkey.

The antipyrine (AP) test has been challenged in species other than humans on the grounds that, in some nonhuman species, particularly on induction, hepatic blood flow may become as prominent a factor in AP clearance as hepatic metabolism. Therefore, we investigated in dogs and monkeys the disposition of AP to determine how well AP serves as a model drug to indicate changes in rates of hepatic clearance. After administration of an oral solution of AP (5 mg/kg) to control dogs, the percentage of the dose absorbed was 98%, based on urinary and fecal excretion of AP and its metabolites. Despite complete AP absorption, absolute bioavailability of AP was 78 +/- 12% under basal conditions, suggesting that AP does undergo some degree of presystemic elimination, approximately 22%. After PB administration of 20 mg/kg/day for 9 days, po, AP bioavailability decreased to 60 +/- 14%. The systemic clearance of AP increased from 9.4 +/- 2.3 ml/min/kg under basal conditions to 27.5 +/- 4.6 ml/min/kg following PB. PB decreased mean plasma AP half-life from 71.5 min under basal conditions to 27.7 min, and mean hepatic blood flow increased from 0.49 liters/min to 0.63 liters/min. Induction doubled the hepatic extraction ratio for AP to 0.4 from 0.2 under basal conditions. In beagle dogs after PB pretreatment, 97% of the total systemic clearance of AP was estimated to be due to enhanced hepatic AP metabolism, only 3% to increased hepatic blood flow. Therefore, for dogs under both basal and induced conditions it is concluded that AP clearance reflects predominantly hepatic AP metabolism, being negligibly influenced by hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗