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Prescribing and monitoring of valproate

Pharmacy Department, Springfield University Hospital, 61 Glenburnie Road, London SW17 7DJ

Sir: The authors of a recent paper (Taylor et al, 2000) have drawn much-needed attention to the high prevalence of subtherapeutic treatment of conditions such as mood disorders with carbamazepine or valproate. However, the authors have given much emphasis to the use of drug serum levels in monitoring the use of both these drugs in such conditions.

Personal experience suggests that there are potential pitfalls for the unwary in the interpretation of valproate levels. In particular, in a minority of patients it may be impossible to reach the stated trough threshold level of 50 mg/l, even at daily doses in excess of the licensed maximum and despite supervised compliance.

One possible reason for this is that valproate is highly (about 90%) bound to plasma protein at low body levels, but with increasing doses the binding sites become saturated and free levels rise. More active drug is thereby delivered to the central nervous system (CNS) (Dollery, 1991) without in some cases more than a marginal rise in measured (bound plus unbound) serum levels. This effect should be borne in mind if measured levels do not rise in proportion to a dose increase in a particular case.

Other factors confounding the interpretation of valproate levels include the fact that: the effects in the CNS considerably outlive the detectable presence of the drug in the body, possibly because of active metabolites; there is variable displacement from serum binding sites by free fatty acids; blood samples taken just before a dose may not consistently represent trough levels, because of possible entero-hepatic recirculation and diurnal variation in elimination (Chapman et al, 1982; Dollery, 1991). These factors explain, at least in part, why valproate measurements tend to be unreliable for some clinical purposes.

References

CHAPMAN, A., KEANE, P. E., MELDRUM, B. S., et al (1982) Mechanism of anticonvulsant action of valproate. Progress in Neurobiology, 19, 315-359.[CrossRef][Medline]

DOLLERY, C. (ed.) (1991) Therapeutic Drugs. Vol. 2: Sodium Valproate. Edinburgh: Churchill Livingstone.

TAYLOR, D. M., STARKEY, K. & GINARY, S. (2000) Prescribing and monitoring of carbamazepine and valproate — a case note review. Psychiatric Bulletin, 24, 174-177.[Abstract/Free Full Text]

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This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Armour, D. Search for Related Content PubMed Articles by Armour, D.