BMJ  2004;328:167 (17 January), doi:10.1136/bmj.328.7432.167-a

Letter

Timing of drug treatment is crucial

EDITOR—Taylor in his letter asked if time of administration of ramipril in the HOPE study confounds the interpretation.¹ Those prescribing and those designing protocols for clinical trials should be asking at what time of day any drug is best taken. Patients with progressive kidney failure may be "responders" and stabilise kidney function with medication; but others are "nonresponders" progressing to dialysis or death.

Shaw, Davies, and I said in 1963 that deterioration might be a consequence of little or no fall in sleeping blood pressure.² I now often prescribe ramipril, and other drugs, as nocturnal or divided (night and morning) doses for patients who continue to progress. Most patients who presented with progressive kidney failure to my practice are now stabilised or improving.³ I have urged clinicians and clinical trialists to be more thoughtful about the time of administration of drugs in relation to biological rhythms, including the circadian cycle.⁴

Investigators and clinicians in all specialties should give more consideration to the relevance of chronobiology to therapeutics. Bosch et al should answer Taylor's question: "What time was ramipril taken by patients in the HOPE study?"⁵

Mildura Nephrology, 186 Thirteenth Street, Mildura, VIC 3500, Australia mknapp{at}mbox.com.au

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Competing interests: None declared.

References

1. Taylor R. Conundrum of the HOPE study. BMJ 2003;327: 681-2. (20 September.)[Free Full Text]
2. Shaw DB, Knapp M, Davies DH. Changes in the blood pressure of hypertensives during sleep. Lancet 1963:1: 797-8.[CrossRef][Medline]
3. Knapp MS. An audit of pre-dialysis renal failure in a non-metropolitan clinic. Nephrology 2003:8(suppl): A90.
4. Knapp MS. Chronotherapeutics; a new clinical science. BMJ 1978;1: 137.
5. Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002;324: 699.[Abstract/Free Full Text]

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