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Biomedical subjects

W J Westlake

Publications and source records attributed to W J Westlake.

18 recordsLinked to original sources
PubMed1979

Statistical aspects of comparative bioavailability trials.

The role of comparative bioavailability trials in testing for the bioequivalence of different formulations of a drug is discussed and the statistical aspects of the design and analysis of such trials are reviewed. It is suggested that the design of such trials presents no special problem but that the customary method of analysis, which tests the null hypothesis of no difference between the formulations, is irrelevant to the central purpose of such trials, which is to determine whether the formulations have essentially equivalent therapeutic effects. It is proposed that only those characteristics of the data that possess a meaningful relation to the therapeutic use of the drug should be analysed and also that estimation procedures rather than hypothesis testing techniques should be employed. Several aspects of the statistics of bioavailability trials which require further investigation are listed.

Biological Availability↗
PubMed1978

Bioavailability of cimetidine in man.

The bioavailability of parenteral cimetidine was tested in 12 volunteers in a balanced three-way crossover study. Blood levels and urinary excretion were compared after intramuscular and intravenous injection and oral administration of 300 mg of cinetidine. The results indicated that the intramuscular and intravenous routes are virtually interchangeable for parenteral cimetidine, and that the oral liquid, although exhibiting a reduced area under the blood level curve as compared with the parenteral doses, nevertheless demonstrated equivalence with respect to the time the blood level remained above 0.5 microgram per ml. The 300-mg cimetidine tablet formulation was found in another group of 12 volunteers to be bioequivalent to a 300-mg dose of oral liquid.

Administration, Oral↗
PubMed1976

Symmetrical confidence intervals for bioequivalence trials.

The conventional method of setting confidence intervals for the difference of the means of two normal populations gives an interval which is not, in general, symmetrical about zero. A modification of the conventional method which leads to symmetry about zero is discussed and is recommended as particularly appropriate for use in bioequivalence trials. This modification has the effect of decreasing the "effective" length of the confidence interval, on which the decision concerning bioequivalence is based, while increasing the confidence coefficient.

Methods↗
PubMed1975

Statistical problems in interpreting comparative bioavailability trials.

The basic purpose of a comparative bioavailability is to determine whether or not a new formulation of a drug is equivalent in its in vivo behavior to some standard formulation. Statistical analysis of the blood or urine concentrations of the drug plays a critical role in this determination, and two major problems are in deciding what to analyse and what statistical methods to use. It is proposed that the analysis usually employed, namely, hypothesis-testing, is largely irrelevant to the problem and should be replaced by an approach based on confidence intervals. Secondly, it is suggested that only those characteristics of the bood or urine-level sequence that have a meaningful relationship to the therapeutic use of the drug, should be analysed.

Biological Availability↗
PubMedDate not supplied

Steady-state lithium blood level fluctuations in man following administration of a lithium carbonate conventional and controlled-release dosage form.

A controlled-release lithium carbonate tablet was compared to an immediate release lithium carbonate capsule in normal volunteers. These crossover studies at steady state showed that the tablet produced a smoother serum curve than the capsule with no loss of total bioavailability. Quantitatively, the capsule produced about 1.4 times more fluctuation in serum lithium values than the tablet.

Adult↗