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Biomedical subjects

H E Barber

Publications and source records attributed to H E Barber.

At least 37 records · Page 2Linked to original sources

The effect of hydrocortisone phosphate, methylprednisolone and phenytoin on pancreatic insulin release and hepatic glutathione-insulin transhydrogenase activity in the rat.

Following i.v. injection of glucose to rats, blood was collected from the carotid artery and the portal vein, and insulin was determined by radioimmunoassay. Pancreatic insulin release and hepatic insulin extraction were increased following the administration of glucocorticoid drugs and reduced following phenytoin. Hepatic glutathione-insulin transhydrogenase activity (GITA) was measured in each animal and found to be increased after glucocorticoid therapy but unaffected by phenytoin. In alloxan-diabetic rats, GITA was significantly increased following treatment with both methylprednisolone and phenytoin compared with control alloxan-diabetic rats. This is suggestive evidence that both these drugs can initiate an increase in GITA. It is concluded that the markedly raised GITA in steroid-treated non-diabetic rats is the combined result of a drug-induced effect plus the major inducing effect of an increased hepatic uptake of insulin on insulin degradation, whereas the main effect of phenytoin is a reduction of pancreatic insulin release.

Animals↗

The effect of codeine phosphate on the absorption of ethyl alcohol.

The effect of syrup, B.P. and codeine phosphate syrup, B.P.C. on blood alcohol levels was determined in six normal subjects. 2 Treatment with syrup alone had little or no influence on the concentration of ethanol in blood. 3 In contrast, pretreatment with codeine phosphate syrup significantly reduced alcohol absorption, as assessed by the maximum blood levels achieved or the area subtended by the blood concentration-time curve. It is suggested that the diminished absorption of ethanol is related to the pharmacological action of codeine on the stomach. 4 It was considered that the concentration of ethanol in linctuses or syrups containing codeine was unlikely to have any significant effect on the central nervous system.

Codeine↗

Bioavailability and dissolution of different formulations of oxytetracycline preparations.

1 The concentration of oxytetracycline in plasma was studied by microbiological assay after oral administration of five different preparations of the antibiotic. None of these preparations had been studied previously. 2 There was a statistically significant correlation between the time required for 50% dissolution at pH 2 and biological availability, as assessed by the peak plasma level or the area under the plasma concentration-time curve. 3 The mean bioavailability of oxytetracycline was greatest with preparations of the hydrochloride, and with film-coated tablets of the dihydrate. In contrast, sugar-coated tablets of oxytetracycline dihydrate were associated with poorer dissolution characteristics and reduced biological availability.

Biological Availability↗

The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration.

1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug.

Animals↗

The pharmacokinetics of neostigmine and 3-hydroxyphenyltrimethyl- ammonium in the rat: dose-dependent effects after portal vein administration.

1 The elimination kinetics of [(14)C]-neostigmine iodide and [(14)C]-3-hydroxyphenyltrimethyl-ammonium iodide (3-OH PTMA) have been studied in the rat.2 The presence of a renal secretory pathway for neostigmine and 3-OH PTMA has been confirmed.3 For neostigmine and 3-OH PTMA, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that both compounds are subject to extensive metabolism during the first passage through the liver.4 Neostigmine was eliminated by dose-independent kinetics after jugular vein administration but dose-dependent after portal vein administration. In the latter case the fraction eliminated as neostigmine increased with increasing dose. This increase was not accompanied by any change in the fraction of the metabolites eliminated.5 After portal vein administration of 3-OH PTMA, the fraction of the dose eliminated as 3-OH PTMA also increased with increasing dose. This change was accompanied by a decrease in the fraction of the metabolites eliminated which were excreted at a constant rate.

Animals↗

Determination of the renal clearance of inulin in rats: lowered values at low urine flow rates.

The renal clearance of inulin (ClIN) was measured in anaesthetized male rats using a continuous intravenous infusion method.ClIN was independent of urine flow rate provided this was greater than 0.03 ml/minute.At flow rates lower than this, CIIN was reduced and appeared to correlate with the rate of flow.In experiments where a constant kidney function is required. e.g., pharmacokinetic studies, it is advisable to maintain urine, flow rates in the rat above 0.03 ml/minute.

Animals↗

Distribution kinetics and intestinal absorption of practolol in the rat.

1. After intravenous injection of practolol the blood concentration-time curve is fitted by a bi-exponential function. A two compartment open system model is therefore a minimal requirement in order to describe adequately the distribution of the drug in the body.2. The parameters of the two compartment model for practolol were determined. The mean values for the ;fast disposition' half life and the ;slow disposition' half life were 0.5 min and 13.3 min, respectively.3. The rate constants of distribution and elimination were similar in different animals. The volume of the central compartment was related to the weight of the animal.4. The absorption of practolol from an intestinal site was measured by its appearance in the blood. The rate constant for this process was estimated to be 0.03 min(-1).

Acetanilides↗

The use of the logarithmic transformation in the calculation of the transport parameters of a system that obeys Michaelis-Menten kinetics.

1. A logarithmic method is described for the calculation of the transport parameters, K(m) and V(max.)' of a biological system obeying Michaelis-Menten kinetics. 2. This logarithmic method leads to a way of estimating the transport parameters that has not apparently been used previously. It allows the separation of variance due to V(max.) from other variance, and so reduces the fiducial limits that can be placed on an estimation of K(m). 3. The results of studies on the transport of l-histidine and l-monoiodohistidine by rat intestinal sacs in vitro have been used to illustrate the application of the new method. Estimates of the transport parameters have also been made by two alternative procedures. The relative merits of the three methods are discussed.

Animals↗

Mechanism responsible for altered propranolol disposition in adjuvant-induced arthritis in the rat.

Arthritis was induced in Sprague-Dawley rats by the injection of a heat-killed bacterial suspension into the right hind foot pad. The animals were deemed arthritic if their erythrocyte sedimentation rate was greater than 2 mm/hr. A pithed rat preparation was employed to investigate simultaneously the pharmacokinetics and pharmacodynamics of propranolol in this disease state. Propranolol administered via the hepatic portal vein to simulate oral administration resulted in elevated blood concentrations in the arthritic rats, but the pharmacological effect, measured by the inhibition of an electrically induced tachycardia, was not altered. Propranolol administered iv also resulted in increased blood drug concentrations, but, in addition, the pharmacological effect was decreased. Hepatic blood flow was determined in control and arthritic rats using radiolabeled microspheres, but no change was observed. These results, taken together with previous in vitro studies, suggest that the elevated blood concentrations of propranolol can be attributed to increased plasma protein binding, rather than to decreased hepatic metabolism or altered hepatic blood flow.

Animals↗