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PI‐77
Author(s) -
Parasrampuria D. A.,
Gelotte C. K.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.098
Subject(s) - heart rate , pharmacokinetics , medicine , circadian rhythm , adverse effect , stimulant , methylphenidate , chronobiology , anesthesia , ambulatory , cardiology , pharmacology , blood pressure , attention deficit hyperactivity disorder , psychiatry
BACKGROUND Drug effects on heart rate are usually evaluated as percentage change from baseline. Due to inherent circadian variation, these should be evaluated as a function of circadian rhythm and dose. METHODS In an open‐label, pharmacokinetics study, subjects received increasing doses (54, 72, 108 and 144 mg) of OROS methylphenidate HCl for four days each. In addition to pharmacokinetics and safety, heart rate was assessed using two consecutive 48‐hour ambulatory Holter recordings. Heart rate data were averaged over each hour, and modeled using a cosine function. Dose dependence of heart rate was evaluated by determining shifts in parameters (mesor, amplitude, acrophase) describing the cosine wave. RESULTS Twenty‐five subjects completed the study. No serious adverse events were reported. Two subjects (one each in 108 and 144 mg dose groups) withdrew due to adverse events. Modeling indicated a 7.8 beats per minute (bpm) increase in mesor and 5.14 bpm increase in amplitude from 54 to 144 mg. This was statistically significantly different for all treatments (p ≤ 0.0041). Periodicity was significantly different between 144 mg and each lower dose (p ≤ 0.0063), but not for other doses. Traditional analyses of pulse rate data indicated an increase in heart rate of 7 to 15 bpm (144 vs 54), 3 to 10 bpm (108 vs 54), and 1 to 9 bpm (72 vs 54). CONCLUSIONS As expected for a stimulant drug, there was a dose related increase in heart rate and amplitude. Circadian rhythm modeling explains the drug effects more consistently. Clinical Pharmacology & Therapeutics (2005) 79 , P27–P27; doi: 10.1016/j.clpt.2005.12.098