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Biomedical subjects

M D Rawlins

Publications and source records attributed to M D Rawlins.

At least 145 records · Page 8Linked to original sources
PubMed1983

Plasma concentrations of sodium valproate: their clinical value.

Plasma valproate concentrations were monitored prospectively in 54 previously untreated adult patients with epilepsy. Dose and plasma concentration were highly correlated. Adverse effects were common in association with plasma levels above 100 micrograms/ml. In patients suffering tonic-clonic seizures without focal symptoms, no seizures occurred when plasma levels were higher than 50 micrograms/ml. In patients with partial seizures, it was difficult to define a lower limit to a therapeutic range.

Clinical Trials as Topic↗
PubMed1983

The effects of astemizole on histamine-induced weal and flare.

The effect of astemizole on the weal and flare response to intradermal histamine has been studied in normal volunteers after single dosing, and in patients with urticaria and pruritus after chronic dosing with the drug. Single doses of astemizole (40 mg) in normal volunteers significantly reduced histamine weal and flare at 24 and 48 h (p less than 0.001). Before treatment, there was a significantly greater response to intradermal histamine in patients with urticaria than pruritus (p less than 0.05). Chronic dosing with astemizole produced significant reduction in histamine-induced weal and flare in both patient groups which did not show evidence of tachyphalaxis over the period of the study. The effect of astemizole on histamine-induced weal and flare was accompanied by a significant increase in the rate of weal and flare disappearance in both patients (weal p less than 0.002, flare p less than 0.05) and volunteers (weal p less than 0.02, flare p less than 0.005); but there was no change in the rate of weal formation. The effects of astemizole on weal and flare kinetics may be a function of its high level of H1 antagonist activity.

Adult↗
PubMed1983

Lack of effect of astemizole on ethanol dynamics or kinetics.

The effects of astemizole (10 mg daily for 7 days) on the kinetics and CNS depressant activity of ethanol have been examined in a double-blind cross-over study agonist placebo in 7 volunteers. There was no significant change in the elimination rate or AUC of the plasma ethanol concentration-time curve after astemizole. Central nervous system effects of ethanol as monitored by visual analogues of sedation, visual discrimination, pursuit rotor and reaction time were also unaffected by astemizole pretreatment.

Adult↗
PubMed1983

The pharmacokinetics of melphalan in patients with multiple myeloma: an intravenous/oral study using a conventional dose regimen.

The pharmacokinetics of melphalan have been studied after intravenous and oral dosing (10 mg) in 6 patients with multiple myeloma. After intravenous administration, mean plasma t0.5 alpha was 8.0 +/- 2.3 min, t0,5 beta was 63.3 +/- 8.7 min, and total systemic clearance was 510.4 +/- 57.9 ml/min. After oral administration, the drug was rapidly absorbed (lag-time = 18.4 +/- 3.7 min, absorption rate constant = 0.0547 +/- 0.0166 min-1, Tmax = 59.3 +/- 6.6 min), but there was considerable variation in its bioavailability (61.5 - 102.0% mean 78.3 +/- 6.3%). Variability in drug absorption may be responsible, at least in part, for variation in response to this drug.

Administration, Oral↗
PubMed1983

Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites.

Serum concentrations of dihydrocodeine and its acid metabolites have been determined in seven human volunteers (6 male) who received the drug orally (30 mg and 60 mg) and intravenously (30 mg) on separate occasions, and in twenty-four patients (12 male) receiving 25 mg or 50 mg of the drug intravenously. The concentrations were estimated by radioimmunoassay on reconstituted extracts from serum after an extraction process which effectively separates dihydrocodeine from its polar acidic metabolites. The intravenous data show that dihydrocodeine kinetics followed a two-compartment distribution model. The concentration curves after oral administration indicated relatively rapid absorption with mean peak concentrations at 1.6 h-1.8 h. The mean half-lives varied between 3.3 h-4.5 h. From the AUC, the mean bioavailability of orally administered drug was 21% (range 12-34%). The peak levels of the acidic metabolites occurred between 1.8 h-2.0 h after oral administration and 2.2 h-2.5 h after i.v. administration, and they were significantly greater after oral administration. The low bioavailability of dihydrocodeine, together with the earlier and higher plasma levels of the acid metabolites after oral administration is suggestive of substantial first-pass metabolism.

Administration, Oral↗
PubMed1983

The effect of alcoholic cirrhosis on the activities of microsomal aldrin epoxidase, 7-ethoxycoumarin O-de-ethylase and epoxide hydrolase, and on the concentrations of reduced glutathione in human liver.

Activities of the microsomal mono-oxygenases 7-ethoxycoumarin O-de-ethylase (EOC) and aldrin epoxidase (AE), together with microsomal epoxide hydrolase (EH) activity and concentrations of reduced glutathione (GSH) have been measured in liver from patients with alcoholic cirrhosis and in normals. Activities of both mono-oxygenases were significantly reduced in alcoholic cirrhosis. EOC activity (pmol 7-OH coumarin formed/mg microsomal protein/min) was 108.0 +/- 10.6 (n = 8) in normals and 60.9 +/- 11.6 (n = 8) in alcoholic cirrhosis (P less than 0.01). AE activity (pmol dieldrin formed/mg microsomal protein/min) was 58.9 +/- 9.5 (n = 11) in normal liver biopsies and 29.9 +/- 8.6 (n = 9) in alcoholic cirrhosis (P less than 0.05). Microsomal EH activity (nmol styrene glycol formed/mg microsomal protein/min) was similar in normals (39.2 +/- 4.4, n = 11) and alcoholic cirrhosis (40.5 +/- 9.1, n = 6). GSH concentrations (microgram GSH/g liver tissue) were lower (P less than 0.01) in alcoholic cirrhosis (792 +/- 73, n = 10) compared to normals (1182 +/- 76, n = 6).

7-Alkoxycoumarin O-Dealkylase↗
PubMed1983

The acute and chronic effects of H1 receptor blockade with astemizole on indocyanine green clearance.

The effects of acute and chronic (3 months) dosing with astemizole on indocyanine green kinetics have been investigated in normal volunteers and patients. A single dose of astemizole 40 mg produced significant reduction in indocyanine green clearance (P less than 0.02) and volume of distribution (P less than 0.02) when assessed at 48 h, but not at 24 h. In six volunteers who did not receive astemizole there was no significant change in indocyanine green kinetics over a 48 h period. In seven patients on chronic treatment with astemizole there was no significant change in indocyanine green kinetics when these were measured at 1 month and 3 months and compared to pre-treatment values. The change in indocyanine green clearance and volume of distribution following acute astemizole treatment did not correlate with H1-receptor antagonism. Change in indocyanine green clearance following acute drug administration may not be due to changes in liver blood flow and should therefore be interpreted with caution.

Adult↗
PubMed1983

Blood monocyte aryl hydrocarbon hydroxylase activity in psoriasis.

The activity of aryl hydrocarbon hydroxylase (AHH) in monocytes from 13 healthy control subjects and in 16 patients with discoid psoriasis was measured. The mean basal monocyte AHH activities of the control and psoriatic groups were 3.4 +/- 0.47 and 4.46 +/- 0.55 respectively (pmol 3-OHBP h-1 10(-6) cells). This difference was not significant. The mean induced monocyte AHH activities in the control and psoriatic groups were 56.4 +/- 10.8 and 77.8 +/- 16.0 pmol 3-OHBP h-1 10(-6) cells respectively but this difference was not significant. The mean induction ratios in the control and psoriatic groups were 16.5 +/- 1.8 and 20.4 +/- 3.6 respectively. Again, this difference was not significant. We conclude therefore, that monocyte aryl hydrocarbon hydroxylase activity is not reduced in psoriasis.

Adult↗
PubMed1983

Acute dapsone poisoning: clinical features and pharmacokinetic studies.

A case of acute dapsone poisoning in a 57 year old man is reported. Peak plasma dapsone concentrations of 18.8 mg/l were observed 20 hours after ingestion, and methaemoglobin concentrations fell in parallel with dapsone. Plasma dapsone concentrations declined mono-exponentially with time, and the half-life (29.7 hours) was similar to that described in subjects receiving conventional doses. Moreover, the ratio of monoacetyl-dapsone (MADDS) to dapsone remained constant as plasma concentrations fell. These observations suggest that N-acetylation of dapsone was not saturated even at the toxic concentrations observed.

Acute Disease↗
PubMed1982

Predicting the dose of warfarin for therapeutic anticoagulation.

The validity of a previously described technique for predicting warfarin requirements based on the anticoagulant response to a fixed loading dose was assessed prospectively in 57 patients. There was a close relationship between the predicted and initially observed daily warfarin dose required to maintain the patient within the therapeutic range for anticoagulation. The significant relationship between predicted and observed maintenance dose persisted at 4 and 12 weeks although it decreased with increasing time. The relationship between observed and predicted maintenance requirement of warfarin was not affected by the concomitant use of intermittent intravenous injections of heparin when 9 hr was allowed to elapse between the previous dose of heparin and the thrombotest estimation on which the prediction was based. It is concluded that the method is valuable in predicting an individual's warfarin requirement, although it does not obviate the need for regular monitoring of anticoagulant control.

Anticoagulants↗
PubMed1982

Family study of antipyrine clearance.

Antipyrine clearance was measured in 208 healthy volunteers from 78 families. After the values had been corrected for weight and sex, antipyrine clearance was observed to be significantly correlated between siblings (r = 0.590) and between spouses (r = 0.320), but not between parents and their offspring. After the clearance values had been corrected for tobacco and oral contraceptive use, there was still no significant correlation between parents and offspring. These results are incompatible with the hypothesis that antipyrine clearance is primarily determined by genetic factors and indicate that environmental influences predominate.

Adolescent↗
PubMed1982

Propranolol absorption in untreated coeliac disease.

1. To compare the bioavailability and the elimination of propranolol in seven untreated coeliac patients and six normal subjects, plasma concentrations were measured after oral and intravenous propranolol. The bioavailability and clearance of propranolol were similar in both groups. 2. With the use of a perfusion technique, propranolol absorption in the proximal jejunum was found to be decreased by 71% in five untreated coeliac patients, compared with the absorption in four normal subjects. 3. There results indicate that propranolol absorption is decreased in the proximal jejunum in untreated coeliac disease but overall absorption in the small bowel is not impaired.

Absorption↗
PubMed1982

The relationship between individual dietary constituents and antipyrine metabolism in Indo-Pakistani immigrants to Britain.

1 Antipyrine clearance has been measured from serial saliva samples in 36 healthy adult Indo-Pakistani immigrants to Britain, to assess the effect of dietary differences within this population. 2 Clearance (mean +/- s.e. mean) was significantly slower in 16 lactovegetarians (0.54 +/- 0.06 ml min -1 kg -1) than in the subjects who ate meat regularly (0.91 +/-0.07 ml min -1 kg -1). 3 The absence of meat from the diet was associated with a significantly smaller daily intake of dietary protein, which was abnormally low by Western standards. 4 It is likely that the contrast in daily protein intake between the dietary subgroups was largely responsible for the differences observed in antipyrine clearance.

Adult↗
PubMed1982

Efficacy and pharmacokinetics of aspirin in post-operative dental pain.

1 Soluble aspirin, 600 mg and 1200 mg, and placebo were compared in a double-blind, cross-over study in 12 patients with post-operative pain following removal of impacted lower third molars. 2 Significant analgesia after 600 mg aspirin occurred only at 45 min after administration, whereas significant analgesia after 1200 mg aspirin occurred from 45 to 240 min. The 1200 mg dose produced greater analgesia than the 600 mg dose and is to be recommended in clinical practice. 3 Plasma concentrations of salicylate and acetylsalicylate were measured after both doses. A significant correlation (rs = 0.876, P less than 0.01) was observed between analgesia and plasma salicylate concentration after 1200 mg aspirin.

Adult↗