Friday, October 25, 2013

Telaprevir drug monitoring predicts HCV virological response

Telaprevir drug monitoring predicts HCV virological response
Last Updated: 2013-10-24 18:04:08 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Higher trough levels of telaprevir are associated with higher rates of rapid virological response (RVR) and sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV), researchers from Japan report.

"We are ready to begin using these findings in our clinical settings after next month," Dr. Norihiro Furusyo from Kyushu University Hospital, Fukuoka, Japan told Reuters Health by email.

Dr. Furusyo also pointed out that taking telaprevir with meals is associated with higher trough levels.

The analysis of trough concentrations and virological responses involved 70 Japanese patients with HCV genotype 1b, including 20 who were treatment-na�ve, 29 with prior relapse, and 21 nonresponders.

Fifty patients had a rapid virological response (undetectable HCV RNA at week 4), 18 had a complete early virological response (HCV RNA detectable at week 4 but not at week 12), 69 had end-of-treatment responses, and 58 had an SVR, with undetectable HCV RNA at week 24, Dr. Furusyo and colleagues reported online October 3rd in the Journal of Antimicrobial Chemotherapy.

At days 3, 7, and 14, the mean trough level of telaprevir was significantly higher for SVR patients than for non-SVR patients, and the mean trough level of telaprevir was higher for rapid-response patients than for the others (although this difference fell short of statistical significance).

Results were similar in patients with pre-cirrhosis, cirrhosis, and progressive liver fibrosis.

The best predictor of SVR was a trough plasma concentration of telaprevir of at least 1.924 mcg/mL at day 3.

The presence of IL28B (rs8099917) TT allele was also independently associated with SVR.

Among the factors that influence telaprevir levels is whether or not it is taken with meals. Telaprevir concentrations are 73% to 83% lower when the drug is taken under fasting conditions than when it is taken with meals, the researchers note.

How, then, can we increase the levels of telaprevir in these patients? "I have recommend patients with low concentration to take high-fat meals (for example, McDonald's) and then take telaprevir," Dr. Furusyo said. "It is because high-fat meal can increase the levels."

"Even if patients have poor response factors, we, physicians, can increase the response through food educational guidance," Dr. Furusyo said.

Dr. Furusyo added, "Using CYP450 metabolism, we have started a study to increase the levels in combination with statins."


J Antimicrob Chemother 2013.

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