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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