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Biomedical subjects

D P Thornhill

Publications and source records attributed to D P Thornhill.

At least 19 recordsLinked to original sources
PubMed1989

Lack of effect of paracetamol on the pharmacokinetics of chloramphenicol.

The effect of oral paracetamol (1 g) on the pharmacokinetics of oral chloramphenicol (500 mg) was examined in five adult male Zimbabwean patients with normal hepatic and renal function. No significant alteration of half-life, area under the concentration-time curve or peak concentration of chloramphenicol was observed. The previously reported, potentially serious interaction between chloramphenicol and paracetamol administered intravenously was not observed with the more commonly used oral preparations.

Acetaminophen↗
PubMed1986

Serum levels and pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients during chronic dosage.

Ordinary and sustained-release lithium carbonate were administered at approximately equivalent daily dosage (1.5 and 1.8 g = 20.2 and 24.3 mmol ordinary and sustained-release respectively) in a crossover fashion to 5 manic patients. Actual and theoretical steady state serum levels of both preparations were determined. The sustained-release preparation gave observed serum levels that differed widely from predicted levels. Despite larger inter and intra-subject variations the serum levels at commencement and end of the sampling period were fairly constant. The results suggest that the wide individual variations in steady state profiles may be a consequence of the effect of normal physiological variables on drug absorption in the patient/sickness/diet combination of this study. Apparent erratic absorption in some patients, especially with the sustained-release preparation, indicates that great caution should be exercised in deciding when to monitor serum levels as a guide to adjusting dose. A justification is presented for morning sampling time as the most appropriate, regardless of the type of formulation used.

Administration, Oral↗
PubMed1985

STRITERFIT, a least-squares pharmacokinetic curve-fitting package using a programmable calculator.

A program is described that permits iterative least-squares nonlinear regression fitting of polyexponential curves using the Hewlett Packard HP 41 CV programmable calculator. The program enables the analysis of pharmacokinetic drug level profiles with a high degree of precision. Up to 15 data pairs can be used, and initial estimates of curve parameters are obtained with a stripping procedure. Up to four exponential terms can be accommodated by the program, and there is the option of weighting data according to their reciprocals. Initial slopes cannot be forced through zero. The program may be interrupted at any time in order to examine convergence.

Computers↗
PubMed1982

Distribution of lithium elimination rates in a selected population of psychiatric patients.

Chronic treatment with conventional lithium carbonate was interrupted in a selected group of 40 psychiatric patients of mixed sex and race. All patients had normal renal function. Serum samples were taken 12, 24, 36 and 48 h after the last dose and lithium was assayed by atomic absorption spectrophotometry. Decay rates calculated for the 12-24h and 36-48 h periods yielded different values. This was ascribed to the presence of an incomplete redistribution phase during the earlier period. The distribution of elimination rates determined during the later period gave a more symmetrical spread and approximated a normal distribution. The mode, median, mean and standard deviation of the lithium elimination half-lives were 12.5, 14, 18.2 and 7.3h and 22.5, 24.5, 29.8 and 10.1h for the two periods, respectively. The results contrast sharply with another report of the distribution spread of elimination half-lives in a much larger sample. The current values have implications for dosage prediction, serum level monitoring and dosage formulation, especially sustained-release preparations. The evidence was against the possibility that some individuals "retain' lithium.

Adult↗
PubMed1981

The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers.

1 Cefoxitin was given by acute intravenous injection to six healthy volunteers, in a crossover study to investigate the effects of concurrent probenecid administration. 2 Serum antibiotic concentrations were determined by microbiological assay. Cefoxitin concentrations were simultaneously determined in the fluid of blisters produced by topical cantharides. All antibiotic was accounted for in the urine. 3 Cefoxitin was administered by intravenous infusion, subsequent to a loading dose, to produce steady state levels in the region of 10 microgram/ml, in one volunteer. The procedure was later repeated after prior administration of probenecid in the same subject. 4 Pharmacokinetic analyses indicated significant changes only in the parameters associated with renal excretion of drugs. Clearance was reduced by half. 5 The absolute and relative amounts of antibiotic in the central and peripheral compartments were calculated for both modes of administration. In the acute study probenecid produced a small change in distribution away from the peripheral or tissue compartment, towards the central compartment. 6 There was no elevation of initial serum concentrations and sustained levels of antibiotic could be accounted for principally by retarded excretion produced by probenecid, with little contribution by alteration in the disposition of antibiotic. 7 The sustained serum levels of cefoxitin that resulted from its decreased excretion were also reflected in blister fluid. It was concluded that the sustained cefoxitin levels produced by probenecid resulted in similar raised levels in the peripheral or "tissue' compartment, since the redistribution away from the peripheral compartment did not contribute materially to other changes in disposition of drug.

Adult↗
PubMed1979

The pharmacokinetics of diclofenac sodium following intravenous and oral administration.

The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers. After intravenous injection plasma levels of diclofenac fell rapidly and were below the limits of detection at 5.5 h postdosing. Individual drug profiles were described by a triexponential function and mean half-lives of the three exponential phases were 0.05, 0.26 and 1.1 h. After oral doses of enteric-coated tablets, the lag time between dosing and the appearance of drug in plasma varied between 1.0 and 4.5 h. However once drug absorption had commenced similar plasma drug profiles were obtained in different individuals. Peak plasma diclofenac levels ranged from 1.4 to 3.0 microgram . ml-1. The mean terminal drug half-life in plasma was 1.8 h after oral doses. This value was not significantly greater than the value of 1.1 h following intravenous doses. Fifty percent of orally dosed diclofenac did not reach the systemic circulation due, predominantly, to first-pass metabolism.

Administration, Oral↗
PubMed1979

Pharmacokinetics of Bay k 4999, a new broad-spectrum penicillin.

The pharmacokinetics of the broad-spectrum penicillin Bay k 4999 were studied in six healthy male volunteers. A 2-g dose was given by the intravenous route. The tissue penetration of the antibiotic was studied by both dermabrasion and blister techniques. A total of 26.4% of the drug was recovered in the urine in 24 h, 79% of this being excreted in the first 2 h. The elimination half-life in serum was 1.3 h. The dermabrasion levels of Bay k 4999 were generally similar to those in serum, but after 1 h the blister fluid levels of antibiotic were greater than those in serum. Different drug levels obtained by blister and dermabrasion techniques may be due to the different composition of the two fluids.

Adult↗
PubMed1979

Factors affecting the pharmacokinetics of diclofenac sodium (Voltarol).

The blood level curves of diclofenac have been studied following its administration to young and old volunteers, and results of studies performed on olderly patients and those with renal disease are reported. The investigations on young volunteers show that when the enteric-coated tablets are taken there is a delay in the onset of absorption but thereafter absorption and elimination are rapid, with a terminal elimination half-life of 1.2 hours. The relevance of these observations to the patient who is receiving the drug chronically and who is older, ill and often on drugs is discussed. Clearly, all the different factors which may affect the handling of the drug have not yet been evaluated, but the studies carried out so far suggest that the blood level profile obtained is not materially affected by age, renal impairment or chronic administration.

Absorption↗
PubMed1978

Pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients after acute dosage.

An ordinary and a sustained-release lithium carbonate preparation were administered acutely at equivalent dosage (1.80 g = 24.3 mmol) in a crossover fashion to manic patients. Serum lithium levels were determined by atomic absorption spectroscopy and pharmacokinetic parameters were calculated. Maximum mean serum levels of 1.13 mmol/l and 0.78 mmol/l were achieved at 6 h and 12 h respectively with the ordinary and sustained-release forms. The mean half-lives of absorption, redistribution and elimination were 0.78 h +/- 0.05 (SE), 5.06 h +/- 0.23, 26.8 h +/- 4.5 and 3.73 h +/- 0.37 (SE), 4.42 h +/- 0.28 and 25.6 h +/- 5.5 for the ordinary and sustained-release forms respectively. In healthy volunteers the ordinary preparation was completely absorbed but only 85% of the sustained-release form was absorbed in the manic subjects. Lithium ion distributed into two kinetic compartments and the final compartment appeared to correspond to total body water.

Bipolar Disorder↗
PubMed1975

Separation of a series of chromophores and fluorophores present in elastin.

Purified elastin was hydrolysed with HCl and manipulated under conditions that minimized oxidation. Gel-permeation chromatography on polyacrylamide gel and ion-exchange chromatography on dextran cation-exchanger each resulted in the separation of a series of yellow fluorescent fractions. These hitherto unreported ampholytes have fluorescence spectra that approximate to that of the intact protein, and account for its characteristic optical properties. Since the coloured fluorophores are confined to enzyme-resistant regions of the protein molecule they appear to have important structural implications.

Amino Acids↗