ArticleBritish journal of clinical pharmacology2000
The intracellular activation of lamivudine (3TC) and determination of 2'-deoxycytidine-5'-triphosphate (dCTP) pools in the presence and absence of various drugs in HepG2 cells.
Article in British journal of clinical pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 23 citations in OpenAlex.
- Effect of ribavirin on intracellular and plasma pharmacokinetics of nucleoside reverse transcriptase inhibitors in patients with human immunodeficiency virus-hepatitis C virus coinfection: results of a randomized clinical study.Antimicrobial agents and chemotherapy · 2005Trial
- CETSA MS Profiling for a Comparative Assessment of FDA-Approved Antivirals Repurposed for COVID-19 Therapy Identifies TRIP13 as a Remdesivir Off-Target.SLAS discovery : advancing life sciences R & D · 2021Article
- Article
- Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids.Molecular pharmacology · 2015Article
- Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Presteady state kinetic investigation of the incorporation of anti-hepatitis B nucleotide analogues catalyzed by noncanonical human DNA polymerases.Chemical research in toxicology · 2012Article
- Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro.Antimicrobial agents and chemotherapy · 2002Article
- Kinetic analysis of wild-type and YMDD mutant hepatitis B virus polymerases and effects of deoxyribonucleotide concentrations on polymerase activity.Antimicrobial agents and chemotherapy · 2002Article
- Liver Damage During Treatment with Reverse-Transcriptase Inhibitors in HIV Patients.Current health sciences journalReview
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5 authors at 1 institution in 1 country.
Funding
Abstract
aimsLamivudine (3TC, 2'-deoxy-3'-thiacytidine) requires intracellular metabolism to its active 5'-triphosphate, 3TC-5'-triphosphate (3TCTP), to inhibit the replication of hepatitis B virus (HBV). We have investigated the activation of 3TC, in the presence and absence of a range of compounds, in HepG2 cells. The intracellular levels of the endogenous competitor of 3TCTP, 2'-deoxycytidine-5'-triphosphate (dCTP), were also determined and 3TCTP/dCTP ratios calculated.
methodsThe effects of a number of compounds on 3TC (3H; 1 microM) phosphorylation were investigated by radiometric h.p.l.c. dCTP levels were determined using a template primer extension assay. 3TCTP/dCTP ratios were calculated from these results.
resultsThe phosphorylation of 3TC was significantly increased in the presence of either hydroxyurea (HU), methotrexate (MTX), or fludarabine (FLU). For example, at 100 microM HU, control 3TCTP levels were increased to 361% of control, whereas at 100 microM FLU, control 3TCTP levels were increased to 155%. dCTP pools were significantly reduced in the presence of HU and FLU, at 100 microM concentrations only. However, for all the above three compounds investigated, the ratio of 3TCTP/dCTP was favourably enhanced (e.g. at 1 microM MTX, 255% of control). Neither ganciclovir (GCV), lobucavir (LCV), penciclovir (PCV), adefovir dipivoxil (ADV), nor foscarnet (FOS) had any significant effects on 3TC phosphorylation or dCTP pools.
conclusionsThese results suggest that the activity of 3TC may be potentiated when combined with one of the modulators studied. The lack of an interaction between 3TC and the other anti-HBV agents is reassuring. These in vitro studies can be used as an initial screen to examine potential interactions at the phosphorylation level.
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