Evidence map›Paper›PMID 20573083›Full record

ArticleBritish journal of clinical pharmacology2010

Intracellular and plasma steady-state pharmacokinetics of raltegravir, darunavir, etravirine and ritonavir in heavily pre-treated HIV-infected patients.

Rob Ter Heine, Jan Willem Mulder, Eric C M van Gorp, Jiri F P Wagenaar, Jos H Beijnen, Alwin D R Huitema

Open access · bronzeAbstract read
In one paragraph

Article in British journal of clinical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 48 citations in OpenAlex.

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  12. Drug transporters in tissues and cells relevant to sexual transmission of HIV: Implications for drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2015
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Rob Ter HeineDepartment of Pharmacy & Pharmacology, Slotervaart Hospital, Amsterdam, the Netherlands. rob@terheine.nl
Jan Willem Mulder
Eric C M van Gorp
Jiri F P Wagenaar
Jos H Beijnen
Alwin D R Huitema
Slotervaartziekenhuis · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimTo study the steady-state plasma and intracellular pharmacokinetics of raltegravir, etravirine, darunavir and ritonavir in heavily pre-treated patients.

methodsPatients on a salvage regimen containing raltegravir, etravirine, darunavir and ritonavir were eligible for inclusion. During a 12 h dosing interval plasma and peripheral blood mononuclear cells were collected. Drug concentrations were measured using a validated LC-MS/MS assay and pharmacokinetic analysis was performed using non-linear mixed effect modelling.

resultsIrregular absorption was observed with raltegravir and darunavir, which may be caused by enterohepatic cycling. Relative bioavailability of ritonavir was low, when compared with other ritonavir regimens. Raltegravir plasma pharmacokinetics showed wide interpatient variability, while intracellular raltegravir concentrations could not be detected (<0.001 mg l(-1) in cell lysate). The intracellular to plasma ratios for etravirine, darunavir and ritonavir were 12.9, 1.32 and 7.72, respectively, and the relative standard error of these estimates were 16.3%, 12.3% and 13.0%.

conclusionsThe observed distinct intracellular accumulation indicated that these drugs have different affinity for the cellular compartment. The relatively high intracellular accumulation of etravirine may explain its efficacy and its previously described absence of PK-PD relationships in the therapeutic concentration range, when compared with other non-nucleoside reverse transcriptase inhibitors. Lastly, the intracellular concentrations of ritonavir seem sufficient for inhibition of viral replication in the cellular compartment in PI-naive patients, but not in patients with HIV harbouring PI resistance.

Indexed as

Anti-HIV AgentsDarunavirDrug InteractionsDrug Therapy, CombinationHIV InfectionsHumansIntestinal AbsorptionMaleMiddle AgedNitrilesPyridazinesPyrimidinesRitonavirSalvage TherapySulfonamidesAnti-HIV AgentsDarunaviretravirineNitrilesPyridazinesPyrimidinesRitonavirSulfonamides

Identifiers

PMID20573083
PMCPMC2856048
OpenAlexW1569413592

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.