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Biomedical subjects

M L Orme

Publications and source records attributed to M L Orme.

At least 55 records · Page 3Linked to original sources
PubMed1986

Pharmacokinetics of naproxen in elderly patients.

The pharmacokinetics of naproxen have been examined in 13 elderly patients (mean age 84.2 years) and in 9 younger patients (mean age 53.9 years) at the end of a 21 day course of therapy with naproxen 500 mg b.d. The mean pre-dose concentration on days 19, 20 and 21 was significantly higher in the elderly patients than in the controls (60.1 vs. 43.3 micrograms X ml-1). The AUC (0-24) was significantly higher in the elderly subjects only when normalized for body weight (9.1 vs. 5.4 micrograms X ml-1 X h kg-1 p less than or equal to 0.02). The AUC was significantly higher in the elderly group compared to the control group also in the normalized form. The apparent clearance of naproxen was reduced in the elderly compared to the control patients (315 vs. 628 ml X h-1). The percentage protein binding of naproxen was the same in both groups (99.8%) but the free concentration of naproxen was significantly higher in the elderly patients than in the control patients (141 vs. 89.8 ng X ml-1). Although there was no excess of side effects in the elderly patients it is suggested that when naproxen is given to elderly patients, therapy should be started at the lower end of the dosage range.

Adult↗
PubMed1986

The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids.

Patients taking anticonvulsants such as phenobarbitone, phenytoin and carbamazepine together with their oral contraceptive steroid may suffer contraceptive failure because of the enzyme-inducing properties of these anticonvulsants. We have examined, in six women, the effect of sodium valproate, an effective broad spectrum anticonvulsant, on the area under the plasma concentration versus time profile (AUC) of ethinyloestradiol (EE2) and levonorgestrel (Ng). Prior to sodium valproate therapy the mean AUC for EE2 was 880 +/- 109 pg/ml X h (+/- S.E.) and for levonorgestrel it was 29.1 +/- 2.9 ng/ml X h (n = 4). Between two and four months after sodium valproate therapy the mean AUC figures had not changed significantly, the figure for EE2 being 977 +/- 130 pg/ml X h and for levonorgestrel 29.2 +/- 1.9 ng/ml X h (p greater than or equal to 0.1 in each case). We conclude that sodium valproate in the dose used (200 mg b.d.) does not interact with oral contraceptive steroids.

Adolescent↗
PubMed1986

The bioavailability of ethinyloestradiol and levonorgestrel in patients with an ileostomy.

The bioavailability of ethinyloestradiol and levonorgestrel has been studied in 5 young women with an ileostomy following surgery for ulcerative colitis and compared to that in 5 control subjects. Single i.v. and oral doses of both drugs were administered and the bioavailability calculated from the ratio of the two areas under the plasma concentration versus time curve for the two drugs. The mean bioavailability of ethinyloestradiol in the patients with an ileostomy was 55.4 +/- 10.9% (+/- S.D.) compared to a control value of 45.0 +/- 6.1% (p greater than or equal to 0.1). The mean bioavailability of levonorgestrel in the ileostomy patients was 85.2 +/- 13.1% compared to 104.6 +/- 22.3% in the controls (p greater than or equal to 0.1). Women who have an ileostomy following lower bowel surgery can rely on their oral contraceptive preparations being absorbed in the normal way.

Adult↗
PubMed1986

Contraceptive steroid concentrations in women with early active schistosomiasis: lack of effect of antischistosomal drugs.

Plasma concentrations of the oral contraceptive steroids (OCS) ethinyloestradiol (EE2) and levonorgestrel (LNG) have been determined in women with early active schistosomiasis and compared to those obtained in healthy volunteers. Steroid concentrations following a single dose of Ovral (500 micrograms LNG, 50 micrograms EE2) or during a multiple dose regimen were unaffected by the disease. There was no significant effect of the antischistosomal drugs praziquantel (40 mg X kg-1) or metrifonate (10 mg X kg-1 X 3 at 2-week intervals) on plasma steroid concentrations. In regular users of OCS, significantly higher concentrations of LNG were observed than in women who received only a single dose. We conclude that there is no pharmacokinetic reason for withholding OCS from patients with early active schistosomiasis who are also receiving either praziquantel or metrifonate.

Adolescent↗
PubMed1986

Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest.

Plasma concentration profiles and pharmacokinetic parameters have been obtained following single dose administration of three commonly used oral contraceptive steroid preparations, Ovral, Nordette and Norminest to Egyptian women. The constituents of the preparations are as follows: Ovral (50 micrograms ethinyloestradiol, EE2 and 500 micrograms levonorgestrel, LNG); Nordette (30 micrograms EE2 and 150 micrograms LNG); and Norminest (35 micrograms EE2 and 500 micrograms norethisterone, NOR). Peak plasma concentrations of EE2 ranged between 116-160 pg ml-1 for Ovral, 55-78 pg ml-1 for Norminest and 30-70 pg ml-1 for Nordette. There was no significant difference in half-life (t1/2), oral clearance (CL) or apparent volume of distribution (Vd). The relative values of the area under the plasma concentration-time curve (AUC) reflected well the different amounts of oestrogen in each preparation. There was no significant difference in t1/2, CL or Vd for LNG in the 2 preparations containing this progestogen. The mean AUC following Nordette (150 micrograms LNG) was 40% of that following Ovral (500 micrograms LNG; p less than 0.001). Comparing pharmacokinetic parameters for the same dose of LNG (Ovral) and NOR (Norminest) showed the AUC to be decreased and CL and Vd increased in the latter group. The study indicates that the kinetic profile of the OCS in healthy Egyptian women are similar to other ethnic populations.

Adult↗
PubMed1986

The effect of moderate urine alkalinisation on low dose diethylcarbamazine therapy in patients with onchocerciasis.

Twenty-one patients with moderate to heavy infections with O. volvulus were treated with 25 mg of diethylcarbamazine (DEC) citrate twice daily for 10 days. In 11 patients the urine was made alkaline with sodium bicarbonate, 2 g, administered 6 hourly for three doses daily beginning 1 day before DEC was started and continued throughout the DEC therapy. Ten patients served as controls. The mean pre-dose plasma DEC concentration during treatment and the mean plasma DEC half-life were significantly higher in bicarbonate treated patients as compared to controls. Total urinary excretion of DEC was significantly less in the bicarbonate treated group than in controls. Mean overall total reaction was higher in bicarbonate-treated patients but the difference was not significant. The bicarbonate-treated group achieved a significantly greater reduction in skin microfilarial counts than the control group as assessed 1 week after completion of therapy, but there was little difference at 1 month. Microfilarial killing was associated with microfilarial mobilisation, alteration in peripheral leucocytes and elevation in serum aminotransferases in both groups. There was no effect of DEC on the number of adult worms recovered in nodules removed at the end of the therapy. This study indicates that moderate urinary alkalinisation alters the kinetics of DEC and the therapeutic response. However the severity of clinical reaction coupled with the inadequate level of microfilarial killing achieved make it unlikely that manipulation of urinary pH will be of practical value in onchocerciasis chemotherapy.

Adolescent↗
PubMed1985

The debendox saga.

Explore the source record for details and available documents.

Abnormalities, Drug-Induced↗
PubMed1985

Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size.

The pharmacokinetics of primaquine have been examined in five healthy volunteers who received single oral doses of 15, 30 and 45 mg of the drug, on separate occasions. Each subject received an i.v. tracer dose of [14C]-primaquine (7.5 microCi), simultaneously with the 45 mg oral dose. Absorption of primaquine was virtually complete with a mean absolute bioavailability of 0.96 +/- 0.08. Elimination half-life, oral clearance and apparent volume of distribution for both primaquine and the carboxylic acid metabolite were unaffected by either dose size, or route of administration. The relationships between area under the curve and dose size were linear for both primaquine (r = 0.99, P less than or equal to 0.01) and its carboxylic acid metabolite (r = 0.99, p less than or equal to 0.01). The mean whole blood to plasma concentration ratios were determined for primaquine (0.81), and for the carboxylic acid metabolite of primaquine (0.84). Primaquine is a low clearance compound (CL = 24.2 +/- 7.4 l h-1), is extensively distributed into body tissues (V = 242.9 +/- 69.5 l) and is not subject to extensive first pass metabolism.

Adult↗
PubMed1985

Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects.

We have investigated the pharmacokinetics of primaquine after acute and chronic administration of the drug to five healthy Thai volunteers. After acute dosage (15 mg p.o.) mean (+/- s.d.) peak plasma concentrations of 65.0 +/- 34.7 ng ml-1 were achieved within 2 +/- 1h. Thereafter plasma drug concentrations declined monoexponentially with a mean elimination half life of 4.4 +/- 1.4 h. The mean (+/- s.d.) oral clearance was 37.6 +/- 15.5 1 h-1. These values are in broad agreement with values obtained in healthy Caucasians after administration of an equivalent dose of primaquine. Repeated dosing with primaquine had no effect on the mean pharmacokinetic parameters calculated for this drug. In contrast, individual pharmacokinetic parameters for some subjects exhibited gross and unpredictable changes after chronic dosage. The carboxylic acid metabolite of primaquine accumulated in plasma after repeated dosing such that by day 14 of chronic dosing the mean AUC (0,24) for this metabolite was 74% greater than that obtained after acute administration of primaquine.

Humans↗
PubMed1985

The pharmacokinetics of antipyrine in patients with graded severity of schistosomiasis.

The pharmacokinetics of antipyrine have been studied in patients with schistosomiasis. In comparison to a control group of subjects (n = 6), patients with early (active) schistosomiasis (passing live ova in urine or stools without clinical and laboratory evidence of liver involvement; n = 6) exhibited similar pharmacokinetic parameters. Of seven patients with hepatosplenic schistosomiasis (exhibiting hepatic fibrosis, splenomegaly, at least one episode of haematemesis, ascites), five showed markedly enhanced antipyrine half-life and reduced clearance. Compared to controls, the mean half-life of this group was increased from 10.9 +/- 2.4 to 19.9 +/- 9.5 h (mean +/- s.d.; P less than or equal to 0.05) and clearance reduced from 3.81 +/- 0.74 to 2.18 +/- 0.80 l h-1 (P less than or equal to 0.01). There was no change in the apparent volume of distribution. Liver biopsy was performed on all patients diagnosed as having hepatosplenic schistosomiasis in the 2 weeks prior to the antipyrine study. The results of this study indicate that hepatic microsomal metabolism is impaired in patients with advanced hepatosplenic schistosomiasis.

Adult↗
PubMed1985

Influence of urinary pH on pethidine kinetics in healthy volunteer subjects.

The kinetics of intravenous pethidine (150 micrograms kg-1) were determined in 10 healthy Caucasian subjects under uncontrolled and controlled (acidic and alkaline) urinary pH. Although large variations in the 48 hr urinary recovery of pethidine and norpethidine (26.9 +/- 5.9% & 23.4 +/- 4.6%, 0.6 +/- 0.3% & 3.6 +/- 1.6%, 6.9 +/- 3.2% & 17.4 +/- 6.6%, respectively, under acidic, alkaline and uncontrolled urinary pH were induced by change in urinary pH, the terminal t1/2 (7-8 hr), the AUC and the plasma concentration-time profiles were not affected. Under all these conditions, the disappearance of pethidine from the plasma was described by a triexponential function. A 3-compartment open model with input into the central compartment and elimination from both the central and the fast accessible (metabolising) compartment was proposed to interpret pethidine distribution in the body. This model explains the complimentary elimination of pethidine by renal excretion and metabolism. Under alkaline urinary pH, the hydrolytic route predominates as recovery of pethidine and norpethidine in the urine is significantly lower under this condition. Acidification of the urine may increase body clearance of the unchanged drug due mainly to greater renal clearance, and this may be useful clinically to treat acute pethidine poisoning and when the complimentary hepatic metabolism is impaired.

Adult↗