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S M Harding

Publications and source records attributed to S M Harding.

At least 55 records · Page 3Linked to original sources
PubMed1985

Pharmacokinetics of the third-generation cephalosporins.

The pharmacokinetics of 10 of the newer, third-generation cephalosporins are reviewed. Important features are tabulated. Generalizations are made about structure-activity relationships, relationships between kinetic features, minimal inhibitory concentrations, dosage regimens, and tissue penetration. Tissue levels of ceftazidime are given as examples. These newer chemotherapeutic agents do not possess unique pharmacokinetic properties, but a combination of high antimicrobial activity, safety, and straightforward kinetics facilitates their use in a number of different clinical settings.

Animals↗
PubMed1984

The absolute bioavailability of oral cefuroxime axetil in male and female volunteers after fasting and after food.

Cefuroxime axetil is a novel oral cephalosporin. Two studies are described in which fasting male and female volunteers were given single oral doses of 1 g cefuroxime axetil in comparison with intravenous cefuroxime, and in which absorption was compared in the fasting and non-fasting states. The mean (and range) absolute bioavailability of cefuroxime axetil in the first study was 0.35 (0.26-0.44) in male volunteers and 0.32 (0.23-0.41) in female volunteers. In the second study, the bioavailability was significantly greater when cefuroxime axetil was given after food: 0.45 (0.34-0.55) in males and 0.41 (0.29-0.51) in females. There were no differences between the pharmacokinetics of cefuroxime axetil in males and females. It is recommended that patients take doses of cefuroxime axetil shortly after food.

Administration, Oral↗
PubMed1984

Pharmacology of Cefuroxime as the 1-acetoxyethyl ester in volunteers.

Cefuroxime axetil is a new orally absorbed prodrug of the antibiotic cefuroxime. The results of pharmacological studies in 52 healthy volunteers are presented. Intact cefuroxime axetil was not detected in the systemic circulation, indicating that deesterification to yield cefuroxime occurs rapidly after absorption. The bioavailability as measured by urinary recovery of cefuroxime was 40 to 50% if the drug was taken after food and 30% if the drug was taken after overnight fasting. Absorption was similar for three different formulations at 500 mg and independent of dose over the range of 250 mg to 1 g. When the drug was taken after food, serum levels and urinary recoveries were significantly greater for cefuroxime than for ampicillin, but when the drug was taken after fasting the values were similar for the two drugs. The kinetic behavior of cefuroxime axetil and ampicillin was not influenced by repeated dosing at 250 mg. Cefuroxime axetil was well tolerated. Although changes in bowel flora and habit were noted during repeated dosing, these changes were no greater than with ampicillin.

Absorption↗
PubMed1984

Pharmacokinetics and tolerance of cefuroxime axetil in volunteers during repeated dosing.

A total of 158 volunteers each received 21 repeated oral doses of 500 mg of cefuroxime axetil (CAE) during four comparative cross-over trials. Pharmacokinetics were studied in 8 volunteers (CAE versus ampicillin), relative bioavailability and tolerance were studied in 100 volunteers (CAE versus pivmecillinam and CAE versus pivampicillin), and tolerance alone was studied in 50 volunteers (CAE versus ampicillin). Overall, urinary recoveries of the active antibiotics ranked absorption of the drugs in the order least to greatest: pivmecillinam, ampicillin, CAE, and pivampicillin. The pharmacokinetics of CAE and ampicillin did not change after repeated dosing. Peak serum levels of cefuroxime were significantly higher than those of ampicillin after doses 1 and 21 but the urinary recoveries of both antibiotics were around 35% of the dose. CAE was as well tolerated as ampicillin but there were smaller numbers of episodes of fluid bowel motions on pivmecillinam and pivampicillin than on CAE, which may have been due to the smaller amounts of active antibiotic in the doses of the pivaloyloxymethyl esters.

Adolescent↗
PubMed1984

A comparison of pulsed ultrasound, radiography and micrometer screw gauge in the measurement of skin thickness.

Comparisons of ultrasonic, radiographic and micrometer methods in the measurement of skin thickness were made in 16 volunteers before and after 1-month's treatment with four clobetasol propionate formulations. Correlations between the methods were highly significant (r = 0.68 to 0.75). Correlations in the females were better than in the males suggesting that measurements in women are more easily made. Percentage reductions in skin thickness after steroid treatment were ranked in an identical order, whichever method was used. Each of the three methods, therefore, was shown to be effective. Ultrasound was the preferred technique but the micrometer screw gauge was shown to be a reasonable alternative.

Adult↗
PubMed1983

The pharmacokinetic behaviour of ceftazidime in man and the relationship between serum levels and the in vitro susceptibility of clinical isolates.

The pharmacokinetic properties of ceftazidime in volunteers and in vitro activity against a wide range of human pathogens were investigated. Ceftazidime was well tolerated by i. m. and i. v. routes in single doses of 500 mg to 2 g and in repeat doses of 2 g tds for ten days. The half-life averaged 1.9 h and urinary recovery over 24 h averaged 83%. There was good agreement between HPLC and microbiological assay and no metabolites were detected by either method. Correlation of serum levels with MIC90 values suggested that the 500 mg i. m. dose given bd should be suitable for fully sensitive enterobacteria and 1 g i. m. or i. v. bd should be effective against most genera. It may be necessary to use 1 g or 2 g i. v. doses tds when treating infections due to Staphylococcus aureus, Pseudomonas aeruginosa or Acinetobacter spp. These higher doses may be required when there is impaired penetration into the site of infection, when the infection is complicated by underlying pathology or in a life-threatening situation.

Adult↗
PubMed1983

Pharmacokinetics of ceftazidime in male and female volunteers.

The pharmacokinetic behavior of ceftazidime was assessed after single bolus intravenous injections of 1 g to 12 male and 12 female volunteers. The kinetic handling of the drug was essentially identical in the two sexes, exhibiting two-compartment model characteristics. However, the peripheral compartment volume of distribution of ceftazidime was smaller in the females (mean 3.95 liters, compared with 6.15 liters), and this was attributed to a smaller extracellular fluid volume. Eight volunteers in each group also received single 1-g doses of ceftazidime into the vastus lateralis and gluteus maximus muscles. The time to peak concentration was longer in the women, and it was longer after injection into the gluteus maximus in both sexes, presumably because of differences in local blood flow. The bioavailability of ceftazidime may have been slightly reduced by delays in absorption. Again, body and renal clearances were similar for both sexes when allowance was made for differences in distribution volume.

Absorption↗
PubMed1982

Comparison of the bioavailabilities and anticoagulant activities of two warfarin formulations.

Changes in the British Pharmacopoeia dissolution time requirements have necessitated reformulation of warfarin sodium ('Marevan'). The old and new formulations were compared with each other in eight healthy volunteers given a single 15 mg dose of each in a cross-over study and also in 19 patients receiving warfarin therapy. In the volunteer study, a significant but small increase in bioavailability was observed for the new formulation. However, the effects of the two formulations on the prothrombin ratio and on clotting factors II, VII, IX and X were not significantly different. Irrespective of formulation, the greatest changes in factors II, VII and X were observed after the first dose of warfarin. With factor IX, the greatest response was observed after the second dose. The clinical study in patients confirmed that the old and new formulations of Marevan are interchangeable on a dose for dose basis. A sensitive semi-automated warfarin assay technique is described.

Adolescent↗
PubMed1982

Simultaneous comparison of three methods for assessing ceftazidime penetration into extravascular fluid.

The penetration of ceftazidime, a new broad-spectrum cephalosporin, into fluids from subcutaneous threads, suction blisters, and cantharidin blisters was studied in eight healthy male volunteers. A pharmacokinetic analysis showed fundamental differences between the models. The results obtained with the subcutaneous thread technique were similar to those of the peripheral compartment and were characteristic of a rapidly equilibrating compartment. The results obtained with the suction and cantharidin blister techniques were characteristic of slowly equilibrating compartments. We concluded that although one model will not accurately predict the penetration of an antibiotic in all clinical situations, each model will have its own particular application.

Adult↗
PubMed1980

GR 20263, a new broad-spectrum cephalosporin with anti-pseudomonal activity.

GR 20263 is a new broad-spectrum injectable cephalosporin which is stable to most beta-lactamases. Its in vitro activities were of the same order as those of cefotaxime against most gram-negative bacteria, were clearly inferior to cefotaxime against Staphylococcus aureus, but were significantly more active against Pseudomonas aeruginosa. Against the 25 strains used, GR 20263 was significantly more active than any of the other agents tested: piperacillin, azlocillin, gentamicin, amikacin, and carbenicillin. GR 20263 protected mice against experimental infections with P. aeruginosa more effectively than other beta-lactam antibiotics; its general effectiveness in this test was comparable with gentamicin. Studies on human volunteers showed that it produces high, long-lasting blood levels, with much of the antibiotic being recovered in the urine. Intramuscular and intravenous injections were well tolerated by the volunteers, and there were no untoward side effects.

Adult↗
PubMed1978

A comparison of oral and inhaled steroids in patients with chronic airways obstruction: features determining response.

Two trials comparing aerosol and oral steroid treatment were carried out in patients with chronic airways obstruction. All patients had a history of chronic productive cough and an FEV1 less than 70% predicted but did not have episodic or seasonal breathlessness with wheezing. One trial involved 18 outpatients, the other 18 inpatients. Both studies involved three consecutive treatment periods, the first with placebo aerosol, the second with active aerosol (betamethasone valerate, 800 microgram/day), and the third with oral prednisone or prednisolone (30 mg/day). Six patients showed a significant improvement in ventilatory capacity on steroids. Initial assessment included a comprehensive history using a questionnaire, skin tests, blood and sputum eosinophil counts, and chest radiography. In addition, for the inpatients, response to isoprenaline, daily sputum volume, and PaCO2 were measured. Only blood eosinophilia and variability in ventilatory capacity during the placebo period seemed indicative of a likely response to steroids. However, there was a large overlap between various features on assessment in the responders and non-responders, and the management of every patient with chronic airways obstruction should include a controlled trial of steroids. The steroid aerosol produced a good improvement in ventilatory capacity in the responsive patients who were hospitalised and this was thought to be helped by supervision of aerosol technique. Such an aerosol could therefore be used for a steroid trial although oral steroids were found to give a more definitive response.

Administration, Oral↗
PubMed1977

Betamethasone valerate aerosol in the treatment of oral lichen planus.

Betamethasone valerate aerosol, given in doses of up to 800 microgram per day, was compared with placebo in a double-blind trial involving 23 patients with oral lichen planus. The majority of patients receiving the active aerosol noted improvement within the first 2 weeks of treatment and at 8 weeks the lesions had almost cleared; in contrast, only 2 patients on placebo showed slight improvement over the same time period. The results suggest that this form of treatment is an effective and acceptable method of controlling the discomfort due to oral lichen planus, especially where minor erosions are present.

Adult↗
PubMed1976

Intranasal steroid aerosol in perennial rhinitis: comparison with an antihistamine compound.

Intranasal betamethasone valerate aerosol, given for 28 days, was compared with an oral antihistamine compound in a couble-blind, double-dummy, cross-over trial involving thirty patients with perennial rhinitis. The steroid aerosol was more effective in reducing symptoms and was preferred by the patients (P less than 0-01). Nasal blockage index, calculated from oral and nasal peak expiratory flow measurements, did not provide useful or additional information. There were no side effects from the steroid and Candida albicans was not cultured from nasal swabs. It is concluded that beta-methasone valerate aerosol is a suitable short-term alternative for patients whose perennial rhinitis fails to respond to conventional therapy.

Administration, Intranasal↗