PubMed Health⌕ Search

Biomedical subjects

P N Bennett

Publications and source records attributed to P N Bennett.

At least 37 records · Page 2Linked to original sources
PubMed1984

Lignocaine kinetics in the rat.

After intravenous injection of lignocaine 2.5, 5.0 or 10.0 mg kg-1 in the rat blood concentration declined in a bi-exponential m anner. The data were analysed according to a two-compartment open model with elimination from the central compartment. Analysis of variance revealed no significant differences in k12, k21, k13, t 1/2 alpha, t 1/2 beta, AUC or in the volume constants for the different doses used. After lignocaine 50.0, 70.0 or 90.0 mg kg-1 by mouth there was no significant change in t 1/2 beta for the different doses or in peak plasma concentration normalized for dose. For both routes of administration blood concentration-time curves were superimpossible and AUC was linearly related to dose. Renal excretion was negligible. Systemic availability of lignocaine was the lowest of species so far studied (mean 0.019 +/- 0.001) did not alter with dose, and was very similar to the values in the literature quoted for the isolated perfused liver. Clearance of lignocaine related to anticipated liver mass was almost identical to the values for liver blood flow quoted using other techniques. The data indicated high hepatic extraction of lignocaine by the intact rat and the absence of dose dependency within the range studied.

Administration, Oral↗
PubMed1984

Influence of route of hepatic administration on drug availability.

The work investigates functional variability of hepatic arterial and portal venous streams in relation to drug availability. In an isolated rat liver system perfused in all experiments at a constant total flow of 10 ml X min-1, drug availability was found to be 18 and 3 times greater for lidocaine and meperidine, respectively, when infused through the hepatic artery compared to portal vein administration. When both hepatic artery and portal vein were perfused, drug availability increased log linearly for lidocaine, and linearly for meperidine with increasing hepatic artery flow contribution. Injection of 15-micron gamma-labeled microspheres into the hepatic artery and portal vein did not reveal arteriovenous or portovenous shunting channels greater than 15 micron in diameter. However, the ratios of the mean transit times of albumin and red blood cells were found to be significantly lower through the hepatic artery, indicating a possible reduction in perisinusoidal albumin space. When both hepatic artery and portal vein were perfused, linear correlations were obtained for values of this ratio plotted against increasing hepatic artery flow contributions. Data from the red blood cell transit time studies, as well as data on lidocaine availability, suggest the presence of functionally separate capillary beds for the hepatic arterial and venous streams.

Albumins↗
PubMed1983

Models of hepatic drug clearance: discrimination between the 'well stirred' and 'parallel-tube' models.

The predictive ability of two models of hepatic drug clearance are compared. The 'parallel-tube' model predicts that the steady-state drug concentration following constant rate oral administration increases with increase in hepatic blood flow. The 'well-stirred' model predicts that this parameter is not sensitive to changes in hepatic blood flow. Using the steady-state reservoir drug concentration as the discriminatory index, the predictions of the models were tested in a recirculating isolated perfused rat liver system with lignocaine and pethidine, both of which are highly extracted, as test drugs. The steady-state reservoir concentration of both drugs was found to be constant when flow through the liver was increased from 10 ml min-1 to 15 ml min-1. The experimental findings indicate that the 'well-stirred' model more accurately describes the elimination of highly cleared drugs with perturbations of flow than does the 'parallel-tube' model.

Animals↗
PubMed1982

Pharmacokinetics of lidocaine and its deethylated metabolite: dose and time dependency studies in man.

The concentrations of lidocaine and of its deethylated metabolite, MEGX, were measured in blood following the intravenous administration of 50 and 100 mg lidocaine hydrochloride, the oral administration of 100, 300, and 500 mg lidocaine hydrochloride monohydrate, and the oral administration of 300 mg lidocaine hydrochloride monohydrate every 8 h for seven doses, to three healthy volunteers. The range of values for the parameters defining the disposition kinetics of lidocaine were: terminal half-life, 50-231 min; total clearance, 13-17 ml/min/kg; initial dilution space, 0.13-2.5 liters/kg; and volume of distribution at steady state, 0.6-4.5 liters/kg. Lidocaine absorption from solution was rapid, but due to presystemic hepatic metabolism, the availability was low, the range of average values lying between 0.19 and 0.38. No dose or time dependency in lidocaine and monoethylglycinexylidide pharmacokinetics following the single dose studies of lidocaine were noted. Effective hepatic blood flow, based on total clearance and availability measurements, was estimated to be 18-27 ml/min/kg. The concentrations of MEGX were approximately one-third of those of lidocaine following intravenous lidocaine and were comparable following oral lidocaine, but as predicted, the dose normalized area under the MEGX concentration-time curve was constant and independent of the route of administration of lidocaine. In two subjects, the blood concentrations of lidocaine and MEGX following multiple doses of oral lidocaine were those predicted from the single dose studies. In the third subject, the degree of accumulation of lidocaine was greater than predicted. The reasons and mechanism for this difference between subjects on multiple dosing remains unclear.

Administration, Oral↗
PubMed1982

Effect of rifampicin on metoprolol and antipyrine kinetics.

1 Effects of rifampicin on the pharmacokinetics of single oral doses of metoprolol and antipyrine are reported. 2 Rifampicin, administered daily for 15 days, reduced the area under the plasma concentration-time curve (AUC) of metoprolol but the rate constant for elimination (beta) of metoprolol from plasma did not alter significantly. 3 Administration of rifampicin for 13 days reduced AUC and increased beta of antipyrine. Thirteen days after discontinuing rifampicin. AUC and beta of antipyrine remained significantly different from the initial values. 4 Some loss of beta-adrenoceptor blockade should be anticipated if rifampicin is administered to patients who are receiving metoprolol.

Adult↗
PubMed1981

Differential induction of antipyrine metabolism by rifampicin.

Antipyrine is oxidised to three main metabolites in man. There is evidence that the different metabolites are products of different forms of cytochrome P-450. The effect of rifampicin administration for two weeks on the rates of formation of these metabolites was investigated in healthy volunteers. Rifampicin increased antipyrine clearance and shortened its half-life. Two weeks after stopping rifampicin the induction had largely been reversed. Clearance to all three metabolites was increased by rifampicin. Clearance to 3-hydroxymethylantipyrine was increased from 7.8 +/- 0.9 ml/min to 13.3 +/- 1.3 ml/min, to norphenazone from 5.8 +/- 0.6 ml/min to 19.3 +/- 2.1 ml/min and to 4-hydroxyantipyrine from 14.3 +/- 2.2 ml/min to 21.9 +/- 3.9 ml/min. Thus clearance to norphenazone was increased to a much greater extent than to either of the other two metabolites. It is concluded that this provides evidence for the involvement of at least two different forms of cytochrome P-450 in antipyrine metabolism in man.

Adult↗
PubMed1978

Pre-medication for endoscopy. A trial of atropine, pentazocine or pethidine as a supplement to diazepam.

The effects of giving atropine, pentazocine or pethidine, 30--45 minutes before intravenous diazepam have been assessed and compared with a control group given diazepam alone in a double-blind controlled trial of pre-medication for upper gastrointestinal endoscopy involving 143 patients and 6 endoscopists. Atropine or pentazocine increased the success rate of the procedure (p 0.007) but gave no other definite benefit. Pethidine improved the degree of sedation (p 0.01) and the success rate (p 0.007); the combination of pethidine given before diazepam ranked first of all the four treatment regimes. The patients' opinion of the procedure correlated with the duration of endoscopy and the experience of the endoscopist.

Adult↗
PubMed1975

Clinical trials.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed1975

A double blind trial of carbenoxolone and geranyl farnesyl acetate in gastric ulcer.

57 patients with a chronic gastric ulcer were treated as outpatients in a double blind comparison of carbenozolone 100 mg three times daily with the same dose of geranyl farnesyl acetate (Gefarnate). Healing rates for carbenoxolone were better than for gefarnate, but not significantly so. Nearly half the carbenoxolone-treated patients developed hypokalaemia or oedema, whereas no similar side-effects were found with gefarnate. Gefarnate, while not as effective as carbenoxolone, does appear to promote gastric ulcer healing. Its virtual absence of side-effects makes it a safe and useful drug.

Carbenoxolone↗
PubMed1975

Effect of diazepam on unstimulated and on stimulated gastric secretion.

The effect of intravenous diazepam on unstimulated and on pentagastrin-stimulated gastric secretion has been studied in normal subjects. No significant effect of diazapam was found on pentagastrin-stimulated gastric secretion. Unstimulated secretion was reduced by diazepam. This action of diazepam may be useful in peptic ulcer therapy.

Adult↗