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J S Cridland

Publications and source records attributed to J S Cridland.

18 recordsLinked to original sources
PubMed1989

Reporting results from a clinical pharmacological laboratory using a microcomputer.

Responsibility lies with an analytical pharmacological laboratory to issue each result with an assessment of its validity for the corresponding patient. This is scarcely possible by the usual manual methods of data handling even when complete diagnostic and pharmacokinetic data are available, because of the staff time required. Use of a microcomputer running a suite of True Basic programs showing "artificial intelligence" solves the temporal difficulty and leads to the issue of more incisive, detailed reports.

Clinical Laboratory Information Systems↗
PubMed1987

Prizidilol. Metabolism by cytochrome P-450 and acetyltransferase.

The hepatic microsomal cytochrome P-450 enzyme system bound and metabolized the experimental drug prizidilol. Prizidilol bound to two distinct sites on cytochrome P-450. At low concentrations (less than ca 20 microM), prizidilol bound to the substrate binding site of the enzyme and produced a Type I difference spectrum. At higher concentrations (25-190 microM), prizidilol bound to the oxygen binding site of the enzyme and produced a type II difference spectrum. Prizidilol stimulated hepatic microsomal CO-inhibitable NADPH oxidation. Prizidilol metabolism by hepatic microsomes assessed by prizidilol disappearance was inhibited by CO:O2 (80:20; v/v), SKF 525-A and metyrapone. Prizidilol disappearance was monitored using a newly developed TLC assay for prizidilol following derivatization with quinolin-3-al. The apparent binding constants (Ks), maximum extents of binding (delta Amax), Michaelis constants (Km) and maximum velocities (Vmax) for the interaction of prizidilol with hepatic microsomal cytochrome P-450 were assessed in rats pretreated or not with the inducing agents phenobarbital, beta-naphthoflavone and pregnenolone-16 alpha-carbonitrile. For the differently pretreated rats the apparent Ks values for the type I site and the type II site and the apparent Km were ca 3 microM, 150 microM and 2 microM, respectively. Apparent Vmax values varied from 20 to 70 pmol per min per mg microsomal protein. The observed effects of induction on the apparent equilibrium constants and maximum extents of binding and metabolism of prizidilol indicate that the forms of cytochrome P-450 induced by phenobarbital, pregnenolone-16 alpha-carbonitrile or beta-naphthoflavone do not play a major role in the metabolism of prizidilol. Prizidilol was also metabolized by hepatic cytosolic N-acetyltransferase. The apparent Km values for prizidilol and acetyl CoA were 0.8 and 22 microM. Apparent Vmax values were 50 and ca 2 pmol per min per mg protein for partially purified transferase and cytosol, respectively. It is concluded that the rates of oxidation and acetylation of this drug would be expected to be relatively low, being limited by low apparent Vmax values for both oxidation and acetylation.

Acetylation↗
PubMed1985

Interpreting drug levels.

The interpretation of drug concentrations in plasma or serum depends on an understanding of drug behaviour. Summaries of the latter are provided for the use of doctors who do not have easy access to pharmacokinetic and pharmacodynamic information. This approach would be vital to a scheme for a nation-wide pharmacological analytical service.

Carbamazepine↗
PubMed1984

The future of analytical pharmacology--a personal view.

The practicalities of and problems associated with extending an analytical pharmacological service into the community at large are presented. Substantial savings as regards productivity and costs of hospitalization should result.

Body Burden↗
PubMed1983

Rectal administration of metronidazole in severely ill patients.

Ten severely ill patients with life threatening sepsis received metronidazole as suppositories and blood concentrations of the drug were measured twice daily over five days. Therapeutic blood concentrations of metronidazole were maintained at all times in all patients. Rectal administration of metronidazole is accepted as effective prophylaxis against infection associated with surgery and as treatment of established infection. This study shows that in gravely ill patients metronidazole administered as suppositories gives perfectly adequate therapeutic serum concentrations of the drug, but that to achieve these concentrations rapidly the first suppository should be given with an intravenous loading dose.

Adolescent↗
PubMed1983

Radical irradiation and misonidazole in the treatment of T2 grade III and T3 bladder cancer.

The results of 2 pilot studies using a new radiation fractionation schedule plus misonidazole (MISO) in the radical radiotherapy of T2 Grade III and T3 carcinoma of the bladder are presented. Forty Gy in 20 daily fractions of 2 Gy was administered to the whole pelvis over 4 weeks followed by 12 Gy in 2 weekly fractions of 6 Gy. These last 2 doses were given after MISO administration. In an initial pilot study (Pilot Study I) MISO was administered orally only. The first two patients received MISO at a dose of 4.5g/m2 orally with each radiation fraction, after which the dose was reduced to 3.0g/m2 because of drug toxicity. In the second pilot study (Pilot Study II) MISO was administered orally at a dose of 3.0g/m2 and intravesically at a dose of 1.0g to 22 patients. The complete response rate at cystoscopy at 6 months in the latter group of patients is 73%, which is significantly better than that of 43% obtained in a retrospective study of historical controls. There have been no late radiation complications in any of the patients nor any MISO toxicity apart from nausea in the patients receiving 3.0g/m2 orally with or without the intravesical MISO.

Administration, Oral↗
PubMed1983

Apparent half-life of excretion of cannabinoids in man.

The apparent half-life of excretion of cannabinoids was calculated from their concentration in the urine of 27 psychotic patients. The best estimate was about 4 days but the range was too wide to be of use in predicting time to total clearance from the body of any randomly chosen patient.

Adolescent↗
PubMed1979

Costs in a clinical pharmacological laboratory.

As a measure of the efficiency of service provided to the Groote Schuur group of hospitals by the Department of Clinical Pharmacology, certain costs were analaysed. The approximate annual cost of routine analytical work was R40 000 $45 000 or 22 000 pounds). The average cost per assy was R9,50 ($11,30 or 5,50 pounds). Closer examination of data showed that the cheapest assays are those done in large batches using an off-line analytical technique such as thin-layer chromatographic densitometry.

Chemistry, Clinical↗
PubMed1978

A novel semiautomated method for the estimation of free fatty acid in serum or plasma.

A modification of the semiautomated assay method of Antonis (1965. J. Lipid Res. 6:307-312) for free fatty acid is presented. Free fatty acids are extracted from serum or plasma into di-n-butyl ether-2-methoxyethanol; the extract is almost free from phospholipids. The acids are analyzed in a portion of extract by a copper soap method using diphenylcarbazide. The extractant, being less dense than water, is easily separated from an aqueous phase both in the extraction of samples and in the assay of copper soaps. The assay is comparable in accuracy with well-tried titrimetric methods and is quicker and easier to operate.

Autoanalysis↗
PubMed1977

Determination of 2,4-diamino-5-(3,4-dichlorophenyl)-6-methylpyrimidine (BW 197U) in human plasma.

A gas-liquid chromatographic method for the measurement of 2,4-diamino-5-(3,4-dichlorophenyl)-6-methylpyrimidine (BW 197U) in human plasma has been developed. After extraction from alkaline medium into ethyl acetate the compound is injected into a gas-liquid chromatograph and measured using a 63Ni constant-current electron-capture detector. The range of concentrations measured was from 10 ng/ml to 10 microgram/ml in plasma. An internal standard was employed and reproducibility between replicates was found to be good. The method has been semi-automated by the use of an auto-sampler controlled by a minicomputer which also processes the data.

Antineoplastic Agents↗