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Biomedical subjects

B Heinzow

Publications and source records attributed to B Heinzow.

29 records · Page 2Linked to original sources
PubMed1986

Interaction between oral hydralazine and propranolol. II. Assessment of altered splanchnic blood flow as the determinant of altered presystemic extraction.

Coadministration of p.o. hydralazine and d-propranolol or dl-propranolol in six conscious dogs caused a significant increase in peak plasma concentration and area under the p.o. plasma concentration-time curve of propranolol (P less than .01, P less than .01, peak plasma concentration; P less than .01 and P less than .05, area under the plasma concentration-time curve; d-propranolol and dl-propranolol, respectively). Coadministration of p.o. hydralazine with p.o. dl-propranolol resulted in a small trend toward an increase in systemic clearance of i.v. dl-[3H]propranolol; however, this did not reach statistical significance (P less than .2, P less than .1, d-propranolol and dl-propranolol, respectively). When a mixture of d-propranolol and 14C-labeled dl-propranolol was administered into the jejunum of seven anesthetised dogs, the absorption into portal vein of the 14C-labeled dl-propranolol paralleled closely that of d-propranolol both in terms of time to peak and absorption as measured by a percentage of total area under the plasma concentration-time curve at an arbitrary time (10 min) postdose. Assessment of hepatic extraction (E) showed similar close parallels (d-propranolol, E = 0.85 +/- 0.02; dl-[14C]propranolol, E = 0.86 +/- 0.03: mean +/- S.E.M., n = 5, P less than .70). Hepatic extraction of propranolol and blood flow in mesenteric artery and hepatic artery were measured in 23 anesthetised dogs given a constant infusion of d-propranolol into portal vein (11 micrograms/kg/min), made up to 6 control and 17 hydralazine-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Interaction between oral hydralazine and propranolol. I. Changes in absorption, presystemic clearance and splanchnic blood flow.

A study was undertaken of propranolol pharmacokinetics in dogs before and after oral coadministration of hydralazine to determine whether interactions described in humans could be reproduced in an animal model. Additionally, physiological parameters considered to be relevant to the pharmacokinetic handling (absorption rate and splanchnic hemodynamics) were studied. Coadministration of oral hydralazine and propranolol in conscious dogs caused an increase in peak plasma concentration ( Cpmax ) and area under the oral plasma concentration-time curve (AUC) of propranolol ( Cpmax = 19.2 +/- 5.8 ng/ml, control; Cpmax = 91.5 +/- 12.8 ng/ml, posthydralazine : AUC = 65.7 +/- 14.6 ng X hr/ml, control; AUC = 152.4 +/- 23.9 ng X hr/ml, posthydralazine : mean +/- S.E.M., n = 5; P less than .01 and P less than .01), without change either in the peak plasma level, time to peak or plasma AUC of [14C] propranolol and metabolites (P greater than .70, P greater than .90 and P greater than .60, respectively) or in urinary recovery (urinary recovery = 39.7 +/- 4.3% dose, control; urinary recovery = 41.8 +/- 6.2% dose, posthydralazine ). When propranolol was administered i.v., hydralazine caused a small (42.3 +/- 18%), but significant (P less than .025), increase in systemic clearance. Oral bioavailability increased from 7.3 +/- 2.1 to 23.6 +/- 5.1% (mean +/- S.E.M., n = 5, P less than .025), hepatic extraction showed correspondingly inverse changes and estimated hepatic blood flow increased from 34.9 +/- 3.8 to 63.3 +/- 10.8 ml/min/kg (P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1983

Cimetidine-procainamide pharmacokinetic interaction in man: evidence of competition for tubular secretion of basic drugs.

The hypothesis that basic drugs can compete for active tubular secretion by the kidney was tested in six healthy volunteers by comparing the single dose pharmacokinetics of oral procainamide before and during a daily dose of cimetidine. The area under the procainamide plasma concentration-time curve was increased by cimetidine by an average of 35% from 27.0 +/- 0.3 micrograms/ml X h to 36.5 +/- 3.4 micrograms/ml X h. The elimination half-life increased from an harmonic mean of 2.92 to 3.68 h. The renal clearance of procainamide was reduced by cimetidine from 347 +/- 46 ml/min to 196 +/- 11 ml/min. All these results were statistically significant (p less than 0.016). The area under the plasma concentration-time curve for n-acetylprocainamide was increased by a mean of 25% by cimetidine due to a significant (p less than 0.016) reduction in renal clearance from 258 +/- 60 ml/min to 197 +/- 59 ml/min. The data suggests that cimetidine inhibits the tubular secretion of both procainamide and n-acetylprocainamide, and, if so, represents the first documented evidence for this type of drug interaction in man. The clinical implications from this study necessitate dosage adjustments of procainamide in patients being concomitantly treated with cimetidine. The interaction is pertinent not only for basic drugs that are cleared by the kidney, but also for metabolites of basic drugs and endogenous substances which require active transport into the lumen of the proximal tubule of the kidney for their elimination.

Absorption↗
PubMedDate not supplied

Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants.

Prenatal exposure to polychlorinated biphenyls (PCBs) was examined by analysis of cord tissue from 435 children from a Faroese birth cohort. Analysis of 50 paired cord blood samples showed excellent correlation with the cord tissue concentration (r=.90). Among 17 neuropsychological outcomes determined at age 7 years, the cord PCB concentration was associated with deficits on the Boston Naming Test (without cues, two-tailed P=.09 not adjusted for mercury; with cues, P=.03), the Continuous Performance Test reaction time (P=.03), and, possibly, on long-term recall on the California Verbal Learning Test (P=.15). The association between cord PCB and cord-blood mercury (r=.42) suggested possible confounding. While no PCB effects were apparent in children with low mercury exposure, PCB-associated deficits within the highest tertile of mercury exposure indicated a possible interaction between the two neurotoxicants. PCB-associated increased thresholds were seen at two of eight frequencies on audiometry, but only on the left side, and no deficits occurred on evoked potentials or contrast sensitivity. The limited PCB-related neurotoxicity in this cohort appears to be affected by concomitant methylmercury exposure.

Child↗
PubMedDate not supplied

Behavioral effects following single and combined maternal exposure to PCB 77 (3,4,3',4'-tetrachlorobiphenyl) and PCB 47 (2,4,2',4'-tetrachlorobiphenyl) in rats.

The present study has compared the neurobehavioral effects of two structurally different PCB congeners or their combination in rats. Time-mated Long-Evans rats received daily injections of the coplanar PCB 77 (3,4 3',4'-TCB: 0.5 or 1.5 mg/kg), the di-ortho-chlorinated PCB 47 (2,4,2',4'-TCB: 1.5 mg/kg) or a congener mixture (0.5 mg/kg PCB 77 + 1.0 mg/kg PCB 47) from day 7 to 18 of gestation. The PCB exposure levels in brain and perirenal fat of dams and offspring were determined by GC/ECD on gestational day 19 (GD 19), postnatal day 21 (PND 21), and PND 45. PCB 77 was accumulated to a smaller degree than PCB 47. On GD 19, PCB 77 was found to a greater extent in the brains of the offspring than in the brains of the dams, whereas the level of PCB 47 was almost the same in dams and offspring. The testing of open-field behavior in male rats on PND 18 and PND 70 revealed an altered distribution of activity with enhanced activity in the inner zone in PCB 77-treated rats compared to all other groups, while the overall activity was not changed. Distance traveled and rearing behavior on PND 340 were elevated relative to controls in all PCB-treated groups, indicating age-related effects of maternal exposure. A step-down passive avoidance task revealed decreased latencies in the PCB 77 and combined exposure groups on PND 80. Only PCB 77-treated animals showed increased latencies on PND 100 on the haloperidol-induced catalepsy test. These results indicate long-term effects of maternal exposure to PCB 77 on emotional and motor functions. At the dose levels used in the present experiments, the two congeners given in combination did not cause additive or synergistic effects. Instead, concurrent exposure to PCB 47 seemed to counteract PCB 77-induced changes in the pattern of activity.

Adipose Tissue↗
PubMedDate not supplied

Comparison of the effects of nitroglycerin administered to rats by different routes.

In pentobarbital-anesthetized rats a comparison was undertaken of the blood pressure lowering effect of nitroglycerin (glyceryl trinitrate, GTN) administered by different routes: jugular vein (i.v.), portal vein (p.v.), peritoneal (i.p.), intrajejunal (i.j.), and sublingual (s.l.). The potency of GTN given by these routes was approximately i.v.:s.l.:i.p.:p.v.:i.j. = 100:20--10:10--5:5:5--2.5. Application of GTN to the visceral peritoneum (i.p.) caused a greater and more prolonged lowering of blood pressure than an injection into the portal vein. We conclude that the capacity of the liver to degrade the active agent during the first passage can be overcome and that a blood pressure response to enterally absorbed GTN could be caused by a prehepatic site of action, i.e., on the splanchnic venous system.

Animals↗
PubMedDate not supplied

[Population exposure to pollutants--selected examples from Schleswig-Holstein].

Environmental health policy aims at protecting human health against toxic, cancerogenic, mutagenic, teratogenic and other damaging influences. Environmental toxicology must assess the risk of environmental pollutants by monitoring exposure, characterising hazards, and proposing preventive measures. Examples of the cooperation between Public Health departments and the Bureau of Environmental Toxicology of Slesvig-Holstein are presented.

Carcinogens↗
PubMedDate not supplied

Uptake and displacement of [3H]-propranolol and [3H]-chlorpromazine in isolated, recirculating perfused guinea-pig lungs.

The pulmonary uptake of tritium labelled propranolol and chlorpromazine and their displacement by amphiphilic drugs has been studied in isolated guinea-pig lungs. Lungs were perfused by recirculation with 60 ml tyrode solution (carbogen gassed, 37 degrees C, 6% hydroxy-ethyl-starch) at a flow rate of 10 ml/min. In uptake experiments, a steady state was reached within 20 min with 95% of 10(-9) M propranolol and 90% of 10(-9) M chlorpromazine removed from the perfusate. Using 10(-4) M propranolol, a saturation process became evident, whereas no concentration dependency was observed for chlorpromazine uptake. Kinetic analysis revealed similar uptake rates, but different capacities for both compounds. In displacement experiments, 10(-9) M propranolol was displaced by 10(-4) M amphiphilic drugs in the order: chlorpromazine greater than propranolol greater than alprenolol greater than tetracaine. No displacement occurred by practolol, indomethacin or phenylbutazone. The results indicate that the lungs have a large binding capacity for amphiphilic drugs. These compounds can interfere with each other, according to their lipophilicity, their steric configuration and charges.

Animals↗