82
Clin. Pharmacokinet. 21 (1) 1991
The authors reply: We agree with Cox and Rubio that the difference in the plasma clearance of alfentanil between younger and older females could be related to hormonal changes, as we pointed out in the discussion section of our article. However, we disagree with their suggestion of changing the title of the study to 'Hormonal Dependence of Alfentanil Pharmacokinetics in Women'. This cannot be con-
cluded definitely from our study. Hormonal dependence must be proven in another study design. On the question about estrogen therapy in the elderly females, the answer is that none of these patients were receiving estrogens.
H.J.M.
LEMMENS
Protein Binding of Phenytoin In their timely article, 'Therapeutic Drug Monitoring of Anticonvulsants: State of the Art' (Choonara & Rane 1990), the authors present a review covering a large number of individual agents. While their advice and suggestions are well taken, I was disappointed to see no mention of the significance of phenytoin protein binding or the physiological role of the unbound portion of serum phenytoin. That patients with renal failure and/or hypoalbuminaemia have a modified range of therapeutic activity has been noted by others (Liponi et al. 1984). This important concept is often overlooked by practitioners adjusting phenytoin doses Drs Choonara and Rane have approved publication of the above letter and waived the right to reply. - Editor
in response to serum concentration values in patients with renal disease.
EARL L. MARBLE
Veterans Administration New York
References Choonara lA, Rane A. Therapeutic drug monitoring of anticonvulsants: state of the art. Clinical Pharmacokinetics 18: 318328, 1990 Liponi DF, Winter ME, Tozer TN. Renal function and therapeutic concentrations of phenytoin. Neurology 34: 395-397, 1984
Clin. Pharmacokinet. 21 (1) 1991
The authors reply: We agree with Cox and Rubio that the difference in the plasma clearance of alfentanil between younger and older females could be related to hormonal changes, as we pointed out in the discussion section of our article. However, we disagree with their suggestion of changing the title of the study to 'Hormonal Dependence of Alfentanil Pharmacokinetics in Women'. This cannot be con-
cluded definitely from our study. Hormonal dependence must be proven in another study design. On the question about estrogen therapy in the elderly females, the answer is that none of these patients were receiving estrogens.
H.J.M.
LEMMENS
Protein Binding of Phenytoin In their timely article, 'Therapeutic Drug Monitoring of Anticonvulsants: State of the Art' (Choonara & Rane 1990), the authors present a review covering a large number of individual agents. While their advice and suggestions are well taken, I was disappointed to see no mention of the significance of phenytoin protein binding or the physiological role of the unbound portion of serum phenytoin. That patients with renal failure and/or hypoalbuminaemia have a modified range of therapeutic activity has been noted by others (Liponi et al. 1984). This important concept is often overlooked by practitioners adjusting phenytoin doses Drs Choonara and Rane have approved publication of the above letter and waived the right to reply. - Editor
in response to serum concentration values in patients with renal disease.
EARL L. MARBLE
Veterans Administration New York
References Choonara lA, Rane A. Therapeutic drug monitoring of anticonvulsants: state of the art. Clinical Pharmacokinetics 18: 318328, 1990 Liponi DF, Winter ME, Tozer TN. Renal function and therapeutic concentrations of phenytoin. Neurology 34: 395-397, 1984
