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T Piepponen

Publications and source records attributed to T Piepponen.

7 recordsLinked to original sources

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↗

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↗

Astemizole in combination with pseudoephedrine in the treatment of seasonal allergic rhinitis.

The efficacy and side effects of once-daily astemizole-D, a combination of 10 mg astemizole and 240 mg pseudoephedrine, were compared with those of twice-daily brompheniramine-D, a combination of 12 mg brompheniramine and 50 mg phenylpropanolamine (Lunerin), in 64 patients with seasonal allergic rhinitis caused by birch pollen. Efficacy was monitored by patient's diary scores, investigator assessments of nasal and eye symptoms and need of rescue medication during the 4-week study period. Both astemizole-D and brompheniramine-D reduced nasal and eye symptoms of allergy. There were no significant differences between the treatment groups regarding obstruction, but brompheniramine-D alleviated symptoms of rhinorrhoea and itchy eyes significantly more than astemizole-D. On the other hand, the patients in the brompheniramine-D group reported dry mouth, tiredness and drowsiness more often than those in the astemizole-D group. The results indicate that the two drugs are effective in the treatment of seasonal allergic rhinitis, but astemizole-D is better tolerated than brompheniramine-D.

Adolescent↗

Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial.

A double-blind, randomized, multi-center, parallel-group study was conducted in Finland to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder. Ninety-eight patients were randomly assigned to treatment with risperidone (n = 48) or zuclopenthixol (n = 50), in variable doses, for 6 weeks. The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively. Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression. Safety assessments included the Extrapyramidal Symptom Rating Scale, UKU Side-Effect Rating Scale, vital signs, body weight and laboratory screening. The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes, with a trend towards greater improvement in the overall severity of symptoms. The onset of action was significantly shorter with risperidone than with zuclopenthixol. Although the general tolerability of the two drugs was comparable, fewer patients experienced extrapyramidal symptoms with risperidone, so that significantly fewer risperidone-treated patients required antiparkinsonian medication.

Acute Disease↗

Efficacy and safety of itraconazole in the long-term treatment of onychomycosis.

Sixty-one patients with a clinical diagnosis of onychomycosis in finger or toe nails were treated with itraconazole 100 mg/day or griseofulvin 500 mg/day for six to nine months. The infective causes were Trichophyton rubrum, Trichophyton mentagrophytes, or Trichophyton violaceum, and in two cases Candida albicans. A total of 27 finger and 390 toe nails were infected. Statistically significant intragroup reductions from baseline symptom severity values were seen at endpoint (month 6 or 9) for both treatment groups for all parameters: colour change, thickness, brittleness and unaffected area. No clinically or statistically significant differences between the treatment groups were seen at endpoint. However, the itraconazole group continued to improve during the follow-up, while the mean symptom severity ratings remained the same in the griseofulvin group. All itraconazole patients and 85% of griseofulvin patients were rated as cured or markedly improved at endpoint. Nineteen out of 26 evaluable itraconazole patients (73%) remained cured during the three month follow-up period, compared with 12 out of 17 griseofulvin patients (71%). The rather large number of drop-outs, especially among griseofulvin patients, makes it difficult to draw definitive conclusions of the symptom recurrence. Two itraconazole patients stopped medication due to an adverse event, compared to four patients in the griseofulvin group. The clinical laboratory data on itraconazole-treated patients did not show any statistically or clinically significant changes. In conclusion, itraconazole was at least as effective as griseofulvin in the treatment of onychomycosis. The itraconazole group continued to improve after the treatment was stopped. The results show that itraconazole 100 mg/day is safe and efficient in the long-term treatment of fungal nail infections.

Adolescent↗

Diazepam loading in alcohol withdrawal: clinical pharmacokinetics.

The pharmacokinetics of diazepam and its major active metabolite, desmethyl-diazepam, following a loading dose of diazepam (fixed oral doses of 20 mg) were studied in 16 patients on alcohol withdrawal. No toxic drug levels were measured irrespective of the amount of diazepam needed on the loading (83 +/- 27 mg on average). The mean elimination half-life of diazepam fell within the range observed in healthy persons after the ingestion of therapeutic doses (5), or it was only moderately prolonged (t1/2 49.7 h). The ageing process was associated with a slightly prolonged half-life of diazepam. Standard liver function tests could not predict the length of the elimination half-life of diazepam. Active drug concentrations remained high during the first 48 h of treatment, followed by a steady decline. On the basis of this study, it seems that diazepam can be safely and effectively used in loading doses in the treatment of alcohol withdrawal.

Administration, Oral↗