Br. J, clin.

Pharmac, (1985), 20 Letters to the Editors 91

AUCoral Guidicelli et al. (1984) and Richer et al. (1984),
F= they found a linear correlation between CLt.tai
AUCiv of captopnil and CL of creatinine. These data are
-AUCtest in a better agreement with the potentiating ef-
FR = fects of chronic renal failure on captopnl-induced
AUCstandard plasma converting enzyme activity blockade and
Since the estimation of V and CL of a drug blood pressure reduction found by Guidicelli et
require knowledge of F, or at least FR, it is not al.(1984), and Richer et al. (1984) and suggest a
possible to calculate the bioavailability after decrease in the dose titration and a prolongation
only a single oral dose. Therefore, the captopril of the dose interval of captopril in proportion to
CL and V indicated by Giudicelli et al. (1984) the decrease in renal failure.
and Richer et al. (1984) are not valid.
F x dose F. Dose G. DERAY
(CL= ;V=
AUC AUC. k Department of Clinical Pharmacology,
Duchin et al. (1982) estimated the CL and V of Vanderbilt University, Nashville, Tennessee
37232, USA
captopril in healthy subjects after an i.v, dose
and in patients with renal impairment (Duchin et Received 2 January, 1985,
al., 1984) after a radiolabelled oral dose, Unlike accepted 8 March, 1985

References
Duchin, K. L,, Pierides, A. M,, Heald, A., Singhvi, Giudicelli, J. F., Chaignon, M., Richer, C., Giroux, B.
S. M. & Rommel, A. (1984). Elimination kinetics Guedon, J. (1984). Influence of chronic renal
of captopril in patients with renal failure, Kidney failure on captopril pharmnacokinetics and clinical
Int., 25, 942--947. and biological effects in hypertensive patients, Br.
Duchin, K. L., Singhvi, S. M., Willard, D. A., Mig- J. clin. Pharmac., 18, 749-759.
dalof, B. H. & McKinstry, D.N. (1982). Captopril Richer, C., Giroux, B., Plouin, P. F., Maarek, B.
kinetics. Clin. Pharmac. Ther., 31, 452-458, Guidicelli, J. F. (1984). Captopril: pharmnacokin-
Gibaldi, M. & L. Perrier, D. (1982). etics, antihypertensive and biological effects in
Pharmacrokinetics, Second Edition, pp. 145. New hypertensive patients. Br. J. clin. Pharmac., 17,
York: Marcol Dekker. 243-250.

Captopril pharmacokinetics and biological and clinical effects

We thank Dr Deray (1985) for his comments on
our two recently published papers in this Joumal
(Richer et al., 1984; Giudicelli et al., 1984).
Indeed, the term 'bioavailability' which was
used should have been substituted wherever it
appeared by 'systemic bioavailability after oral
administration' and free unchanged captopril
CL0to and V values which were published should
have been read as CltIt/F and VIF values. How-
ever, since the CLtot of biologically active capto-
pril metabolites was not investigated in our
studies, one cannot assume that a correlation
would necessarily have been found between free
unchanged captopril CLItt and the potentiating
effects of chronic renal failure on the drug in-
duced plasma converting enzyme activity block-
ade and blood pressure reduction.
J. F. GIUDICELLI & C. RICHER
Service de Pharmacologie Clinique, Hopital de
Bicetre, 78, rue du General Leclerc, 94270 Le
Kremlin-Bicetre, France
Received 4 March, 1985,
accepted 8 March, 1985
92 Letters to the Editors
References
Deray, G. (1985). Captopril pharmacokinetics. Br. J.
clin. Pharmac., 20, 89-90.
Giudicelli, J. F., Chaignon, M., Richer, C., Giroux, B.
Gu6don, J. (1984). Influence of chronic renal
failure on captopril pharmacokinetics and clinical
and biological effects in hypertensive patients. Br.
J. clin. Pharmac., 18, 749-759.
Br. J. clin. Pharmac. (1985), 20
Richer, C., Giroux, B., Plouin, P. F., Maarek, B. &
Giudicelli, J. F. (1984). Captopril pharmacokin-
etics, antihypertensive and biological effects in
hypertensive patients. Br. J. clin. Pharmac., 17,
243-250.

31-adrenoceptor selectivity and intrinsic sympathomimetic

activity

I wish to draw the attention of your readership to
an inaccuracy in the'report by Dahlof et al.
(1984) on the initial clinical experience with ICI
141,292, a new 3-adrenoceptor blocking agent
which simultaneously possesses Pl-adreno-
ceptor selectivity and intrinsic sympathomimetic
activity (ISA).
Dahlof et al. (1984) state that only one such
drug, practolol, was available. This is incorrect;
acebutolol, a 3-adrenoceptor blocking agent
currently registered in most countries of the
world (but not yet in Sweden or Norway),
possesses both Pl-adrenoceptor selectivity and
ISA. I otherwise agree with the authors that a
selective 01-adrenoceptor blocking agent with
ISA appears to offer the ideal combination of
ancillary properties for the treatment of hyper-
tension.
G. G. DE BONO
May & Baker Ltd, Rainham Road South,
Dagenham, Essex RMIO 7XS
Received 4 March, 1985,
accepted 12 March, 1985

Reference
Dahlof, B., Danielson, M., Andersson, O., Thulin,
T., Ohman, P., Morlin, C., Boberg, J., Karlberg,
B. E., Jern, S. & Hansson, L. (1984). Initial clinical
experience with ICI 141,292 (Visacor'*), a new
selective f31-adrenoceptor blocker with ISA-a
multicentre trial in 59 patients. Br. J. clin.
Pharmac., 18, 831-836.

Erratum
Br. J. clin. Pharmac. (1985) 19, 329-333
Timolol and atenolol: relationships between oiddation phenotype, pharmacokinetics and
pharmacodynamics
R. V. LEWIS, M. S. LENNARD, P. R. JACKSON, G. T. TUCKER, L. E. RAMSAY &
H. F. WOODS
The Editors would like to apologise to the authors for a typographical error in the caption to Figure 2
on page 332 which should read:
Figure 2 Percentage 1-adrenoceptor blockade following timolol (a) and atenolol (b) vs time in six extensive (0)
and four poor (0) metabolisers of debrisoquine. Vertical bars represent s.d. *P < 0.01.