Handbook of Clinical PHarmacoki-netic Data (David B. Jack)


Collections of drug data are useful. One of the earliest I remember using was at the back of Smith and Rawlins's Variability in Human Drug Responsel I referred to it almost weekly, often wishing it were longer and more comprehensive. Since then a number of other collections have appeared, usually as appendices to works on clinical pharmacology and pharmacokinetics 2.3


For some time we have needed a pocket collection of pharmacokinetic data and I was pleased to accept the invitation to produce one. I use the word 'produce' intentionally, since there is precious little writing involved although there is a great deal of searching and evaluating. I have gathered data from research papers devoted to single drugs, reviews and larger collections of data.


About halfway through the preparation of this book an excellent little volume

from ADIS Press4 appeared and I was gratified and greatly encouraged by the

measure of agreement between those data and my own.


The material gathered in the present volume should be of use to a variety of

people including medicinal chemists, pharmacists, pharmacologists, clinicians,

trialists and toxicologists. It can be used for theoretical as well as practical purposes. Every effort has been made to make it as up to date as possible while still retaining data on older drugs and those compounds that are no longer used clinically but may still be of use in the laboratory, e.g. benoxaprofen, phenacetin, phenylbutazone and glutethimide.


The use of the individual entries and how they have been constructed is explained below and, in order to keep the size of the book small, compromises inevitably have had to be made.


A collection such as this owes a tremendous debt to the individual researchers

who toiled to produce the original data and their efforts are gratefully acknowledged. Some so-called 'pure' pharmacologists sneer at the work of pharmacokineticists, toiling away to obtain clearance, protein-binding and other data on Drug A, publishing it, then starting all over again on Drug B.


However if you believe, as I do, that many scientific observations are only tiny

pieces of a mosaic whose significance can only be seen when taken as a whole, then their efforts are worth while. The ultimate aim of pharmacokinetics is to allow drugs to be prescribed more safely and effectively. It never seems to occur to many of those' pure' pharmacologists that the study of Drug X in a preparation of cockroach salivary gland (to take an example almost at random), to be followed by a study of  Drug Y under similar conditions, is not all that different in principle, except that

pharmacokineticists are much nearer the patient. You can easily find cockroaches in hospitals - I know because I have worked in some - but none has ever to my knowledge been admitted as a patient.


At the very start I took the decision to rely only on published data rather than

request material from the files of pharmaceutical companies, since the former have at least been subjected to peer review. When one begins to compile a work like this, it soon becomes apparent how few published data there are on some drugs, and for a number of drugs in the BNF no published data exist at all. These are, of course, drugs that reached the market a long time ago when regulations were less demanding; their use, however, has stood the test of time. Nevertheless, in order to use any drug safely and sensibly, we need basic data such as are gathered here.


Fortunately, new agents are now studied in greater detail than ever before and it is encouraging to see more pharmacokinetic studies in the elderly, using frail as well as healthy subjects, and in patients with renal or hepatic disease, in addition to those in young, healthy volunteers. More studies are also appearing examining the pharmacokinetic behaviour of drugs in other diseases such as spinal injury5, bums6 and cystic fibrosis7, and at least one book has been devoted exclusively to pharmacokinetics in the elderly8. These advances are to be applauded.


I have produced what is essentially a 'pharmacokinetic' book, and the clinical

data, by the very nature of medicine, are less precise. However, clinical material has been included to give essential background information and to complement the kinetic data. It hardly needs saying that, for reasons of space, the clinical material is given in only the briefest detail and the doses given in the tables should not be used to prescribe drugs. Texts such as the BNF itself should be consulted.


While every reasonable effort has been made to check the data, mistakes will

inevitably occur and I should be very grateful if these were pointed out; I should also welcome suggestions for the inclusion of other agents.

The drugs have been set out basically according to the system used in the BNF, although one or two minor changes have been made. In a rapidly changing field such as clinical pharmacology this work should be regarded only as a 'snapshot' of the scene.


The selection of any piece of data requires that a decision be made and why

should one choose a particular piece and not another? Take as an example the halflife of an intensively studied drug such as propranolol. If one were simply to search the literature and give a range that included all the half-lives that had ever been reported, the data would be of little help. Representative data should be chosen and outliers, for whatever reason, should be rejected. This is not difficult to do when one has a detailed knowledge of the drug in question, but very few of us can claim a really detailed experience of more than a few compounds. I have been forced to make many decisions throughout the book and I hope that I have been right most, if not all, of the time.


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