Single-dose pharmacokinetics of pediatric and adult formulations of etravirine and swallowability of the 200-mg tablet: results from three Phase 1 studies.
OBJECTIVE
Three studies were conducted to assess the pharmacokinetics, methods of administration and ease of swallowability of etravirine tablets.


METHODS
Two randomized studies in healthy adults investigated the single-dose pharmacokinetics of etravirine in various dosage strengths and the effects of dispersion in water and film-coating. A third study explored swallowability of etravirine 200-mg tablets in HIV-infected patients. First study: 37 volunteers received 1 × 100-mg non-coated tablet (reference), 4 × 25-mg noncoated tablets and 1 × 100-mg non-coated tablet dispersed in 100 ml water. Second study: 24 volunteers received 2 × 100-mg non-coated tablets (reference), 2 × 100-mg coated tablets, 1 × 200-mg non-coated and 1 × 200-mg coated tablet. Pharmacokinetic parameters were determined using non-compartmental analysis and least square means (LSM) ratios and 90% confidence intervals (CI) were calculated. Third study: 49 virologically-suppressed patients already on an etravirine-containing regimen rated the swallowability of two etravirine formulations (200-mg non-coated and 200-mg coated tablets).


RESULTS
In the first study LSM ratios (90% CI) for the etravirine area under the plasma concentration-time curve (AUC) administered either as 4 × 25-mg tablets or 100-mg tablet dispersed were: 0.91 (0.85 to 0.98) and 0.97 (0.90 to 1.03), respectively. In the second study, when comparing a 200-mg non-coated and coated tablet to 2 × 100-mg non-coated tablets, LSM ratios for etravirine AUC were 98 to 99%. In the third study, more patients rated the 200-mg than the 100-mg tablets as acceptable to swallow (70% vs. 43%).


CONCLUSIONS
Comparable etravirine exposures were observed regardless of formulation or method of administration (i.e., dispersion); 200-mg tablets were rated as easier to swallow than 100-mg tablets.
Thomas N
TN
Kakuda
Cindy
C
Berckmans
Goedele
G
De Smedt
Ruud
R
Leemans
Lorant
L
Leopold
Monika
M
Peeters
Steven
S
Nijs
Veerle
V
Vyncke
Rodica
R
van Solingen-Ristea
Richard M W
RM
Hoetelmans
D000328:Adult; D000368:Aged; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002648:Child; D003679:Deglutition; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics*; D013607:Tablets
D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; C451734:etravirine