C P Collier

SickKids, Toronto, Ontario, Canada

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Publications (2)7.72 Total impact

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    ABSTRACT: The pharmacokinetic behaviour of pemoline was studied in 28 children, aged 5 to 12 years, diagnosed as having the attention deficit disorder with hyperactivity. The mean elimination half-life of pemoline in these children was approximately 7 hours, which is considerably shorter than the half-life of 11 to 13 hours previously reported in adults. The tendency of the half-life to increase with age may be explained by the statistically significant decrease in total body clearance with age. The increasing half-life of pemoline with age should be considered during long term drug therapy. In this study no tolerance to the beneficial effects of pemoline was observed over 6 months. The apparent therapeutic serum concentration range for these children was attained after doses of 37.5 to 131.25 mg pemoline daily. Since the optimum serum concentration shows wide variation, the dosing regimen must be determined individually. Routine monitoring of the pemoline serum concentrations is not useful because of this apparent variation in optimum serum concentration and because of the linear relationship between dose and concentration.
    Clinical Pharmacokinetics 01/1985; 10(3):269-78. · 5.49 Impact Factor
  • C P Collier, S M MacLeod, S J Soldin
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    ABSTRACT: The simultaneous analysis of methotrexate (MTX) and its putatively nephrotoxic metabolite, 7-hydroxymethotrexate (7OH-MTX), by high-performance liquid chromatography (HPLC) and ultraviolet spectrophotometric detection is described. Serum extraction employs SEP-PAK C-18 cartridges. Recovery ranges from 78.3 to 84.9% for MTX and 67.6 to 76.1% for 7OH-MTX. Between-day precision studies of serum (controls), containing 2.76 microM MTX and 4.40 microM 7OH-MTX, yielded coefficients of variation of 8.6 and 8.9%, respectively. Reconstitution of the dried residue in 5 mM HCl increases the retention times of 7OH-MTX and MTX, thereby enhancing their separation from extraneous serum peaks. A comparison of MTX levels determined by HPLC and a competitive protein binding assay yielded consistently lower results by HPLC. However, in comparing HPLC to EMIT, two relationships were observed: below 100 microM MTX the methods were in agreement, whereas above 100 microM MTX HPLC again provided lower values. Preliminary pharmacokinetic studies on two patients with osteogenic sarcoma are reported. After receiving 218.2 mg/kg and 148.5 mg/kg MTX in a 6-h infusion, their beta half-lives for MTX were 2.6 and 2.0 h, while their gamma half-lives were 26.2 and 42.9 h, respectively. The 7OH-MTX beta half-lives were 5.8 and 4.0 h, and the gamma half-lives were 10.2 and 15.8 h. Plasma concentration ratios of 7OH-MTX to MTX were 28.5 and 18.1 at 24 h after MTX infusion. 7OH-MTX was detected in the 15-min sample after the beginning of the MTX infusion.
    Therapeutic Drug Monitoring 02/1982; 4(4):371-80. · 2.23 Impact Factor