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Titolo:
Combination therapy with saquinavir soft gelatin capsules in children withhuman immunodeficiency virus infection
Autore:
Kline, MW; Brundage, RC; Fletcher, CV; Schwarzwald, H; Calles, NR; Buss, NE; Snell, P; Delora, P; Eason, M; Jorga, K; Craig, C; Duff, F;
Indirizzi:
Texas Childrens Hosp, Houston, TX 77030 USA Texas Childrens Hosp Houston TX USA 77030 ens Hosp, Houston, TX 77030 USA Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 , Dept Pediat, Houston, TX 77030 USA Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 Pharm, Minneapolis, MN 55455 USA F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland F Hoffmann La Roche & Co Ltd Basel Switzerland CH-4002 asel, Switzerland Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England Roche Prod LtdWelwyn Garden City Herts England AL7 3AY Y, Herts, England Hoffmann La Roche Inc, Nutley, NJ 07110 USA Hoffmann La Roche Inc Nutley NJ USA 07110 Roche Inc, Nutley, NJ 07110 USA
Titolo Testata:
PEDIATRIC INFECTIOUS DISEASE JOURNAL
fascicolo: 7, volume: 20, anno: 2001,
pagine: 666 - 671
SICI:
0891-3668(200107)20:7<666:CTWSSG>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
STAVUDINE D4T; PHASE I/II; ZIDOVUDINE; INDINAVIR; FORMULATION; DIDANOSINE; NELFINAVIR; LAMIVUDINE; EFFICACY; INFANTS;
Keywords:
saquinavir soft gelatin capsules; nelfinavir; human immunodeficiency virus infection;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Kline, MW Texas Childrens Hosp, 6621 Fannin St,MC1-4000, Houston, TX 77030USA Texas Childrens Hosp 6621 Fannin St,MC1-4000 Houston TX USA 77030
Citazione:
M.W. Kline et al., "Combination therapy with saquinavir soft gelatin capsules in children withhuman immunodeficiency virus infection", PEDIAT INF, 20(7), 2001, pp. 666-671

Abstract

Objectives. To evaluate the pharmacokinetics, tolerance, safety and antiviral activity of the HIV protease inhibitor, saquinavir, formulated as soft gelatin capsules (SQV-SGC), given in combination with nucleoside antiretroviral agents (NRTIs) with or without nelfinavir in HIV-infected children. Methods. This was an open label study of HIV-infected children ages 3 to 16 years, conducted in two parts. In Part 1 of the study 14 children were treated orally with SQV-SGC (initially given in three 33-mg/kg doses daily; dosage adjusted to 50 mg/kg three times daily based on initial pharmacokinetics) and two NRTIs, Addition of nelfinavir was permitted for children who did not achieve a predetermined steady state target plasma saquinavir exposure, In Part 2 a new group of 13 children received SQV-SGC (33 mg/kg three times daily) in combination with nelfinavir and one or two NRTIs, Pharmacokinetics were assessed after the first dose and 4 weeks into treatment (steady state). Patients were treated for 72 and 48 weeks in Parts 1 and 2, respectively. Results. Most adverse events were mild; the most commonly reported were diarrhea, abdominal discomfort and headache. Two children were withdrawn fromthe study because of adverse events (one each of nausea and dysphagia) related to the study treatment. There were no deaths or serious adverse eventsattributed to the study medication. Steady state saquinavir area under theplasma concentration vs. time curves (AUC(24)) were 6210 and 11010 ng/h/mlfor Parts 1 and 2, respectively. Compared with baseline measurements median changes in plasma HIV RNA concentrations were -2.12 log(10) copies/ml [5 of 14 (36%) with HIV RNA <50 copies/ml) (Week 72)] and -2.58 log(10) copies/ml [8 of 13 (62%) <50 copies/ml) (Week 48)] in Parts 1 and 2, respectively. The median changes in CD4(+) lymphocyte count were +292 and -1-154 cells/mul for Parts 1 and 2, respectively. Genotypic resistance assays revealed alow frequency of saquinavir-associated resistance mutations after 48 weeksof therapy, with only 2 of 27 children having substitutions at positions 48V and/or 90M. Conclusions. Combination therapy with SQV-SGC was well-tolerated and safe in HIV-infected children, and antiviral activity was observed, Saquinavir plasma concentrations were lower than expected, particularly for Part 1 (SQV-SGC plus NRTIs), but addition of nelfinavir increased saquinavir exposures.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 21:45:06