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Biomedical subjects

M Rowland

Publications and source records attributed to M Rowland.

At least 181 records · Page 10Linked to original sources
PubMed1986

Correlation between in-vitro microsomal enzyme activity and whole organ hepatic elimination kinetics: analysis with a dispersion model.

A new model, the dispersion model of hepatic elimination, is applied to the correlation between in-vitro microsomal data and corresponding rat isolated perfused liver data for a number of drugs reported in the literature, whose extraction ratio varies over the range of 0.01 to 0.995. The dispersion model described the data better than either the 'well-stirred' model or the 'parallel-tube' model, two other widely used models of hepatic elimination. The experimental data support the concept that elimination of solutes is affected by is a considerable dispersion on passage through the liver.

Animals↗
PubMed1986

Efficacy of oral treatment with acyclovir and co-trimoxazole in first episode genital herpes.

Forty patients presenting with first episode genital herpes were randomly allocated to seven day treatment with oral acyclovir alone, placebo alone, oral acyclovir plus co-trimoxazole, or placebo plus co-trimoxazole. Patients receiving acyclovir had significantly shorter periods of viral shedding (p less than 0.001), pain (p = 0.03), and times to lesion healing (p less than 0.05). Averaged over all patients there was no evidence that co-trimoxazole affected any of the variables, though in women cotrimoxazole was associated with a shorter time to lesion healing (p less than 0.01). Furthermore, the combination treatment gave significantly shorter times to lesion healing than acyclovir alone, placebo alone, or placebo and co-trimoxazole (p = 0.01) and good trends elsewhere (external lesions and duration of pain). Neither drug was associated with any adverse events or toxicity or influenced the subsequent recurrence rate.

Acyclovir↗
PubMed1985

Eosinophilic peritonitis: an unusual manifestation of spontaneous bacterial peritonitis.

Eosinophilic ascites is an uncommon clinical entity with diagnostic considerations separate from those of spontaneous bacterial peritonitis (SBP). We describe a man with documented E. coli SBP with an 80% eosinophilia in peritoneal fluid (total cell count 12,400/mm3) and no peripheral eosinophilia. Antimicrobial therapy resulted in both clinical improvement and resolution of the eosinophilia in the ascitic fluid. The possible role of associated medications and the potential importance of this syndrome are discussed.

Ascites↗
PubMed1985

Antipyrine metabolite kinetics in healthy human volunteers during multiple dosing of phenytoin and carbamazepine.

Antipyrine total clearance and the formation clearance of its major metabolites were studied in normal, healthy male volunteers before and after multiple dosing for approximately three weeks with phenytoin (six subjects) and carbamazepine (six subjects). Total antipyrine clearance increased on average by 91% after phenytoin dosing and by 61% after carbamazepine and individual increases correlated well with mean plasma concentrations of the anti-epileptic drug. The increase in total clearance resulted largely from increased formation clearances of the 4-hydroxy and 3-hydroxymethylantipyrine metabolites with minimal effect on the norantipyrine pathway, following treatment with both enzyme-inducing drugs. It is concluded that both phenytoin and carbamazepine have similar effects on antipyrine metabolism and that these effects are mediated by induction of specific forms of cytochrome P450.

Adult↗
PubMed1985

Acyclovir prophylaxis of recurrent genital herpes: randomised placebo controlled crossover study.

Forty patients were entered into a randomised placebo controlled crossover study to assess the efficacy and safety of oral acyclovir 200 mg four times a day in the prophylaxis of recurrent genital herpes. Each treatment began during a recurrence and continued for a maximum of 84 days or until the onset of the next recurrence, when the alternate medication was started. Of 28 patients who completed both treatment courses, only three developed a recurrence while taking acyclovir compared with 26 while taking placebo. The mean time to first recurrence was more than 84 days in patients receiving acyclovir and 24 days in patients receiving placebo (p less than 0.001). The mean time to first recurrence after treatment with acyclovir ceased was 16 days. Adverse events, though thought unlikely to be related to treatment, necessitated the withdrawal from the study of two patients while taking acyclovir and one patient while taking placebo. No clinically important effects on haematological or biochemical variables occurred during the acyclovir treatment. All viral isolates tested after treatment remained sensitive to acyclovir. Acyclovir prophylaxis of recurrent genital herpes is effective and safe but does not appear to influence the natural history of the disease after cessation of 84 days' continuous treatment.

Acyclovir↗
PubMed1985

Influence of fraction unbound upon the renal clearance of furosemide in the isolated perfused rat kidney.

The influence of fraction furosemide unbound (varied over a 28-fold range) upon its renal clearance was studied in an isolated perfused rat kidney, while renal function was maintained. Renal clearance and unbound fraction of furosemide were found to be related linearly, the average unbound renal clearance being 3.3 ml min-1. Urine pH and urine flow rate did not influence furosemide renal clearance in the ranges experienced in this study. Our results are consistent with those predicted from a consideration of the kinetics of renal excretion.

Albumins↗
PubMed1984

Liquid chromatographic determination of lipophilicity with application to a homologous series of barbiturates.

A graphical method for determining the lipophilicity of the members of a homologous series of barbituric acids, from a consideration of their reverse-phase HPLC retention data, is described. The HPLC parameter used as the index of lipophilicity, RQ, is shown not only to form excellent correlations with the more commonly employed indices of lipophilicity, Rm and log P, but also to have a predictive capability for those log P values that had not previously been determined experimentally.

Barbiturates↗
PubMed1984

Stereospecific fluorescence high-performance liquid chromatographic analysis of warfarin and its metabolites in plasma and urine.

A stereospecific assay for the simultaneous determination of the enantiomers of warfarin and its major metabolites, 6- and 7-hydroxywarfarin and warfarin alcohols, in plasma and urine was developed. Involved in this determination was the formation of diastereoisomeric esters with carbobenzyloxy-L-proline, separation by normal-phase high-performance liquid chromatography, and detection by fluorescence after postcolumn aminolysis with n-butylamine. The determination limit for any enantiomer is in the order of 50-100 ng. The method was applied to the analysis of the enantiomers of warfarin and metabolites in plasma and urine of human subjects receiving racemic drug. The results for warfarin enantiomers are comparable with those obtained by an MS method, involving administration of a synthetic pseudoracemate [12C(R), 13C(S)]warfarin. In addition to all known metabolites, the detection of 7-R-hydroxywarfarin indicates that 7-hydroxylation is stereoselective rather than stereospecific.

Chromatography, High Pressure Liquid↗
PubMed1984

Protein binding and hepatic clearance: discrimination between models of hepatic clearance with diazepam, a drug of high intrinsic clearance, in the isolated perfused rat liver preparation.

The influence of protein binding on the extraction ratio, and availability, of diazepam has been examined in the single-pass isolated perfused rat liver preparation. Binding of diazepam was varied by adjusting the concentration of albumin in the perfusate. In the absence of binding the extraction ratio of diazepam was high, 0.93-0.995. Extraction decreased dramatically as the degree of binding was increased. The data are more consistent with the "parallel-tube" model than with the "well-stirred" model, two perfusion models that have been used to describe hepatic drug elimination.

Animals↗
PubMed1984

A simple system for the investigation of protein binding effects on the renal handling of drugs in an isolated perfused rat kidney preparation.

An isolated perfused rat kidney preparation was developed that allowed drug-protein binding in the perfusate to be varied while maintaining renal function. When applied to digitoxin and frusemide, two drugs highly bound to bovine serum albumin, the fraction of drug unbound could be continuously varied over approximately a 30-fold range.

Animals↗
PubMed1984

Recurrences after first episodes of genital herpes in patients treated with topical acyclovir cream.

The effect of topical acyclovir treatment of first episode genital herpes on the time to first recurrence in a group of 42 patients receiving either acyclovir or placebo was investigated. Topical acyclovir treatment had no effect on time to first recurrence in patients with either first episode HSV-1 or HSV-2 infections. There was no significant difference in the time to first recurrence in patients with either true primary or initial genital infections. However, the time to first recurrence in patients with first episode HSV-2 was significantly shorter than in patients with first episode HSV-1. Acyclovir treatment appeared to have no effect on the development of neutralising antibody in patients with either virus type.

Acyclovir↗