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Biomedical subjects

R Oksman

Publications and source records attributed to R Oksman.

2 recordsLinked to original sources
PubMed1999

Continuous and intermittent itraconazole dosing schedules for the treatment of onychomycosis: a pharmacokinetic comparison.

This multicentre, double-blind, randomized study compared the pharmacokinetics of itraconazole given at 200 mg once daily for 3 months and intermittently at 200 mg twice daily for 1 week per month followed by a 3-week drug-free period for 3 months in the treatment of onychomycosis. Patients were followed for 9 months after treatment. Itraconazole and hydroxy-itraconazole plasma concentrations and itraconazole nail tip concentrations were determined at regular intervals. With intermittent therapy (n = 64), increases of consistent magnitude were seen in the mean itraconazole and hydroxy-itraconazole plasma concentrations at the end of each 1-week treatment phase; values returned towards baseline during each subsequent 3-week drug-free period. The mean concentration of itraconazole in fingernail tips increased steadily from week 4, reached a maximum value at week 24 (213 ng/g), declined sharply between weeks 24 and 36 and returned to baseline by week 48; the mean concentration profile was similar for toenail tips (maximum value 305 ng/g at week 24) but decreased at a slower rate. With continuous therapy (n = 65), steady-state mean plasma concentrations of itraconazole and hydroxy-itraconazole were obtained within 4-5 weeks of the start of treatment and remained reasonably constant between weeks 4 and 12. The mean concentration of itraconazole in fingernail tips reached a maximum value at week 12 (524 ng/g) and returned towards baseline by week 48; in contrast, the maximum mean concentration of itraconazole in toenail tips was 698 ng/g at week 36 and did not return to baseline by week 48. No clear relationship was observed between response to treatment and concentration of itraconazole or hydroxy-itraconazole in plasma or itraconazole in nails, suggesting that concentrations exceeded therapeutic levels. In conclusion, intermittent therapy resulted in higher maximum itraconazole plasma concentrations but lower total drug exposure, and hence lower itraconazole nail concentrations, than continuous therapy. However, the intermittent schedule was not associated with a lower cure rate, which indicates that itraconazole nail concentrations remained within the therapeutic range.

Adolescent↗
PubMed1997

A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe-nail onychomycosis.

In this multicentre, double-blind, parallel group study, we evaluated the efficacy and safety of continuous treatment with itraconazole, 200 mg daily for 3 months, in comparison with itraconazole pulse therapy, 400 mg daily 1 week per month for 3 months, in the treatment of toe-nail onychomycosis. The study included 129 patients with distal subungual onychomycosis of the toe-nails, confirmed by microscopy and positive for dermatophyte culture; 65 received continuous treatment and 64 received pulse therapy. Patients were followed up for 9 months after treatment. After 12 months, there were 62 evaluable patients in the continuous group and 59 evaluable patients in the pulse group. The clinical response (i.e. the size of the affected area and the progress of the infection) and mycological cure (i.e. negative results on microscopy and culture) were the main outcome measures. A clinical response was defined as a cure or a marked improvement. Clinical response rates were 69%, in the continuous group, and 81% in the pulse group at month 12; the corresponding mycological cure rates were 66 and 69%. A better improvement in signs and symptoms was noted in the pulse group. Six patients were withdrawn from treatment because of adverse events, not all of which were thought to be drug-related. There were no clinically relevant laboratory abnormalities. We conclude that both regimens are effective, safe and well tolerated. The superiority of one treatment over the other was not established, but the results tended to favour pulse therapy. Equivalence testing confirmed that pulse therapy was at least equivalent to continuous treatment.

Adolescent↗