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Titolo:
Effect of alpha(1)-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir and indinavir in vitro
Autore:
Jones, K; Hoggard, PG; Khoo, S; Maher, B; Back, DJ;
Indirizzi:
Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3GE, Merseyside,England Univ Liverpool Liverpool Merseyside England L69 3GE E, Merseyside,England
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 1, volume: 51, anno: 2001,
pagine: 99 - 102
SICI:
0306-5251(200101)51:1<99:EOAGOT>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS PROTEASE; ACID GLYCOPROTEIN; DISEASE; BINDING;
Keywords:
alpha(1)-acid glycoprotein; HIV; intracellular accumulation; protease inhibitors; U937 cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
14
Recensione:
Indirizzi per estratti:
Indirizzo: Jones, K Univ Liverpool, Dept Pharmacol & Therapeut, New Med Bldg,Ashton St, Liverpool L69 3GE, Merseyside, England Univ Liverpool New Med Bldg,Ashton St Liverpool Merseyside England L69 3GE
Citazione:
K. Jones et al., "Effect of alpha(1)-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir and indinavir in vitro", BR J CL PH, 51(1), 2001, pp. 99-102

Abstract

Aims Since alpha (1)-acid glycoprotein (AGP) levels may be raised during HIV infection, we have examined in vitro the effect of increasing the concentration of AGP on the intracellular accumulation of the HIV protease inhibitors saquinavir (SQV), ritonavir (RTV) and indinavir (IDV). Methods U937 cells (5 x 10(6) cells in 5 mi RPMI growth medium) were incubated at 37 degreesC for 18 h with [C-14]-SQV (0.1 mu Ci), [H-3]-RTV and [H-3]-IDV (0.135 mu Ci) to a final concentration of 1 muM in the presence of 0, 0.5 and 2.0 mg ml(-1) AGP. Following extraction in 60% methanol the intracellular drug concentration was determined by liquid scintillation counting. Results Binding to AGP (2.0 mg ml(-1)) reduced the mean intracellular concentration of SQV from 31.5 muM to 7.4 muM (P<0.0001; 95% CI 19.4-28.8). RTVconcentration was also reduced (8.8 <mu>M to 1.6 muM, P<0.0001; 95% CI 5.4-9.0) as was the concentration of IDV (3.0 <mu>M to 1.5 muM; P< 0.0001; 95%CI 1.1-1.9). Conclusions Reduced intracellular protease inhibitor concentrations in thepresence of increasing concentrations of AGP will certainly impact on the antiviral activity in vitro. However, since protease inhibitors are high clearance drugs, free drug concentration will likely remain unaffected in thepresence of elevated AGP during chronic oral dosing although there will bean increase in total plasma drug concentration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 01:22:05