Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
SINGLE-DOSE AND STEADY-STATE PHARMACOKINETICS OF A NOVEL MICROFLUIDIZED SUSPENSION OF ATOVAQUONE IN HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE PATIENTS
Autore:
DIXON R; POZNIAK AL; WATT HM; ROLAN P; POSNER J;
Indirizzi:
ZENECA PHARMACEUT,CLIN PHARMACOL UNIT,ALDERLEY PK MACCLESFIELD SK10 4TG CHESHIRE ENGLAND WELLCOME RES LABS,DEPT CLIN PHARMACOL BECKENHAM BR3 3BS KENT ENGLAND WELLCOME RES LABS,DEPT STAT BECKENHAM BR3 3BS KENT ENGLAND KINGS HLTHCARE,DEPT GENITOURINARY MED LONDON SE5 9RS ENGLAND KINGS HLTHCARE,DEPT MED LONDON SE5 9RS ENGLAND
Titolo Testata:
Antimicrobial agents and chemotherapy
fascicolo: 3, volume: 40, anno: 1996,
pagine: 556 - 560
SICI:
0066-4804(1996)40:3<556:SASPOA>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
566C80; HYDROXYNAPHTHOQUINONE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
8
Recensione:
Indirizzi per estratti:
Citazione:
R. Dixon et al., "SINGLE-DOSE AND STEADY-STATE PHARMACOKINETICS OF A NOVEL MICROFLUIDIZED SUSPENSION OF ATOVAQUONE IN HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE PATIENTS", Antimicrobial agents and chemotherapy, 40(3), 1996, pp. 556-560

Abstract

The single- and multiple-dose pharmacokinetics of and tolerability toa new microfluidized suspension of atovaquone were studied in human immunodeficiency virus-seropositive patients with CD4 counts of less than or equal to 200 cells per mm(3) in order to define a dosing regimenfor the treatment of Pneumocystis carinii pneumonia, This was an openstudy with groups of six patients each. In the first part of the study, six subjects received escalating single doses of 500, 1,000, and 1,500 mg after an overnight fast at weekly intervals. In the second partof the study, groups of six subjects were dosed for 14 days accordingto three regimens: 1,000 mg twice daily fasting, twice daily with a high-fat meal, or once daily with a high-fat meal, Plasma atovaquone levels were assayed by high-performance liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental methods, and statistical comparison of parameters for single doses was performed by analysis of variance, Plasma drug concentrations increased with single doses from 500 to 1,000 mg but were no higher with a dose of 1,500 mg. Thus, 1,000 mg was selected for multiple administration, A regimen of 1,000 mg twice daily with food resulted in a 93% increase in the average trough steady-state concentration compared with 1,000 mg once dailywith food, Food increased the bioavailability of atovaquone 1.4-fold over that in the fasting state. All patients who received 1,000 mg twice daily with food achieved target steady-state concentrations in plasma of 15 to 25 mu g/ml. Multiple-dose regimens were generally well tolerated, but the higher levels in plasma achieved by 1,000 mg twice daily with food were associated with an increased incidence of rash, In conclusion, target plasma atovaquone concentrations for the treatment of P. carinii pneumonia can be achieved in most patients with 1,000 mg twice daily in a fasting state and in all patients with 1,000 mg twicedaily administered with food, but at higher concentrations in plasma,there may be an increased risk of rash.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 21:53:37