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Biomedical subjects

J R Lowe

Publications and source records attributed to J R Lowe.

36 records · Page 2Linked to original sources
PubMed1981

A pharmacokinetic and tolerance study of Ro13-9904, a new cephalosporin antibiotic.

1 Six healthy male volunteers received a total of 2500 mg of a new cephalosporin antibiotic Ro13-9904 by intramuscular injection in five divided doses at intervals of 12 h. 2 No significant systemic side-effects were observed and this was confirmed haematologically and biochemically. 3 The drug was distributed following intramuscular injection reaching a mean peak plasma concentration of 55 micrograms ml-1 (range 46-66) 1 to 2 h after the first injection. 4 Monoexponential elimination of drug was demonstrated. No significant difference was recorded in the plasma half-life after the initial dose (mean 6.7 h) and at steady state (mean 6.7 h). The half-life is long compared with other cephalosporin antibiotics. 5 On the basis of the observed half-life, steady state should be reached within 48 h. A mean peak plasma concentration of 74 micrograms ml-1 (range 65-87) was recorded at steady state. Steady state plasma concentrations of Ro13-9904 with a dose of 500 mg every 13 h may be predicted from the pharmacokinetics of a single dose.

Adult↗
PubMed1981

Bioavailability of aspirin in the presence of dextropropoxyphene/paracetamol combination.

The effect of 2 doses of a combination analgesic preparation (each dose containing 65 mg dextropropoxyphene hydrochloride and 650 mg paracetamol) upon plasma salicylate concentration after a single dose of soluble aspirin (1.2 g) or enteric-coated aspirin (1.2 g) was examined in 6 normal volunteers and compared with the effect of placebo. The dextropropoxyphene/paracetamol caused no reduction in the plasma salicylate level after absorption of soluble aspirin compared with placebo and, although a reduction in plasma salicylate was seen after enteric-coated aspirin in a single subject, this may reflect erratic absorption rather than a drug interaction.

Acetaminophen↗
PubMed1980

Discriminatory indices of response of patients with rheumatoid arthritis treated with D-penicillamine.

A long-term study is being undertaken to classify drugs used as specific agents in the treatment of rheumatoid arthritis in terms of their effects on biochemical and clinical characteristics of the disease. In particular is hoped to establish those indices which are most relevant to the response of RA to treatment. Fifteen patients were treated with D-penicillamine after an initial period of 2 weeks on aspirin alone, when the baseline investigations were made. The dose of penicillamine was increased gradually to a maximum of 500 mg a day over the period of 6 months, and changes in 8 clinical and 25 laboratory indices were measured on 8 separate occasions in the 6-month period. Marked clinical improvement took place, and this was mirrored by changes in a wide range of biochemical parametaers. ESR and C-reactive protein were shown to be the most suitable indices of disease improvement with penicillamine treatment.

Adult↗
PubMed1979

Prednisolone absorption in coeliac disease.

The pharmacokinetic disposition of prednisolone was studied following oral administration (10 mg) to eight patients with untreated coeliac disease of mild or moderate severity, seven coeliac patients on a strict gluten-free diet and ten normal subjects. No significant differences were shown in the peak prednisolone level, the time of the peak level, the area under the concentration versus time plot, the plasma half-life and the 24 h urinary recovery of prednisolone in the three subject groups. There was however considerable variability within each group. It is concluded that the presence of coeliac disease does not significantly alter the absorption or elimination of prednisolone.

Adult↗
PubMed1978

The bioavailability of benorylate in hot beverages.

It has been recommended that benorylate may be administered with hot beverages to overcome the problem of its relative unpalatability. Urine salicylate recovery used as a measure of bioavailability in 20 normal subjects has shown that hot coffee has no significant effect on drug availability from the orally administered suspension.

Adult↗
PubMed1978

Gamma glutamyl transpeptidase levels in arthritis: a correlation with clinical and laboratory indices of disease activity.

Gamma glutamyl transpeptidase (GGTP) was measured in 62 patients with rheumatoid arthritis (RA) and 27 with osteoarthrosis (OA). The values for GGTP were significantly higher in the subjects with RA compared with the OA group. The prevalence of elevation of GGTP was higher in the RA subjects (77%) than in the OA patients (33%). Levels of GGTP correlated significantly with a number of objective indices of activity of RA in a separate group of 28 patients. Following treatment with penicillamine, GGTP levels showed a significant drop towards normal levels.

Aged↗
PubMed1977

Dose dependent pharmacokinetics of prednisolone.

The pharmacokinetics of prednisolone elimination have been studied in both arthritic patients and normal volunteers using tritiated prednisolone alone, and in conjunction with unlabelled prednisolone in doses of 0.15 mg-kg-1 and 0.3 mg-kg-1 body weight. With increasing dose there is prolongation of the plasma half-life and increase in the volume of distribution and plasma clearance of prednisolone. It is proposed that these changes in pharmacokinetic parameters may be associated with non-linear binding of the steroid to plasma proteins.

Adult↗
PubMedDate not supplied

Temperature effects in cyanolysis using elemental sulfur.

As part of our studies directed at new treatments for cyanide poisoning we examined the effect of temperature on both the non-catalyzed and the albumin-catalyzed reactions of cyanide with a colloidal suspension of elemental sulfur (CSES). Using saturated sulfur solutions prepared in two solvents, pyridine (PY) and methyl cellosolve (MC), the reactions were studied at 15.0, 25.0, 30.0 and 37.5 degrees C. For all the cyanolysis reactions (non-catalyzed and albumin-catalyzed) there is an enhancement of reaction rate when the organic solvent for the sulfur is MC. Irrespective of the solvent for the CSES, the non-catalyzed reactions gave linear Arrhenius plots (PY, correlation coefficient = 0.998; MC, correlation coefficient = 0.997). In each case the entropy of activation was positive (14.1 cal K-1 mol-1 for PY and 56.4 cal K-1 mol-1 for MC). In contrast with these results the albumin-catalyzed reactions generated non-linear Arrhenius plots and negative entropies of activation. Non-linear plots were observed with the three albumins studied: human serum albumin, heat-shock bovine serum albumin and fatty acid-free bovine serum albumin. The non-linear plots are the result of a more complex reaction sequence than a simple cyanolysis reaction.

Colloids↗
PubMedDate not supplied

The effects of food and of antacid on the single oral dose pharmacokinetics of tenoxicam.

A single oral dose (40 mg) of tenoxicam (Ro12-0068) was administered to six normal male volunteers pre- and post-prandially and to a further six volunteers with and without antacid to determine the effect of food and and of antacid on absorption. The rate of absorption was slower with post-prandial than with pre-prandial administration, resulting in a significantly later time for peak plasma drug levels (4.1 h compared to 1.3 h). No effect was evident on the extent of absorption or other pharmacokinetic parameters. Similarly, the rate of absorption was significantly slower after concurrent antacid than without antacid (t1/2 0.47 h compared to 0.18 h) resulting in a later peak time (4.7 h compared to 2.3 h) and significantly lower peak level (4.2 micrograms X ml-1 compared to 5.1 micrograms X ml-1) of parent drug in plasma. Again, no effect was evident on the extent of absorption or other pharmacokinetic parameters. It is concluded that food and antacids both tend to reduce the rate of absorption of tenoxicam, but that the extent of absorption is essentially unchanged. The influence on the overall kinetic profile is relatively minor, and thus unlikely to affect the therapeutic response.

Antacids↗
PubMedDate not supplied

A clinical and biochemical evaluation of Clozic, a novel disease modifying drug in rheumatoid arthritis.

We have compared two dose levels of Clozic, a novel agent with potential anti-rheumatoid activity, to D-penicillamine and aspirin in an observer blind randomised parallel group study of 56 patients with active rheumatoid arthritis. Eight clinical assessments and 26 laboratory assessments were performed on each patient at each visit over a six month period. Results were analysed by conventional methods and also by correlation matrices constructed between clinical and laboratory variables. Patients treated with D-penicillamine (500 mg/day) responded adequately and the control group on aspirin (up to 3.6 g of enteric coated formulation/day) performed well, though the withdrawal rate from this latter group was high, predominantly because of continued disease activity. Patients receiving Clozic (100 mg/day or 300 mg/day) improved more than patients receiving penicillamine, particularly at the higher dose. Comparison of methods of analysis validates the use of correlation matrices both for detecting anti-rheumatoid activity and for determining the optimum dose of a novel compound. This trial illustrates the problems of a study of this nature, with the powerful effect on patients of being enrolled in such a closely monitored investigation. It emphasises the greater value of biochemical changes in following disease changes.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Serum histidine in rheumatoid arthritis: changes induced by antirheumatic drug therapy.

Serum free histidine levels were studied in 15 patients with rheumatoid arthritis treated with D-penicillamine and 15 patients treated with hydroxychloroquine for 6 months. Both drugs produced improvement in the majority of patients, measured in terms of changes in 5 clinical parameters and plasma viscosity. A significant increase in serum histidine was observed only with D-penicillamine. This action, not seen with other specific antirheumatoid drugs may reflect a specific action of the drug.

Adult↗