Page 60 - Book of Abstracts

th
8 Biannual Conference on Chemistry - CHEM 08

Determination of Directly Acting Antivirals in Human Plasma:
Application to Investigating the Significance of Therapeutic Drug

Monitoring and Dose Adjustment in End Stage Liver Disease
Faten Farouk
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian
University, Egypt.
Email: f.farouk04@gmail.com

ABSTRACT

HCV infection is considered a huge burden in patients with end stage renal
disease (ESRD). New direct acting antiviral (DAA) drugs are now available for
these patients. The question remains about the proper time of administration of
these drugs. The aim of this work is to compare the pharmacokinetic (PK) and
pharmacodynamic (PD) properties of DAAs given to patients before and after
dialysis; thus detect the optimum time for administration and to assess the
significance of therapeutic drug monitoring (TDM) in this special population .
1
An HPLC analytical method was developed and validated for the determination
of DAA in human plasma. The method was applied for therapeutic drug
monitoring in HCV infected patients with ESRD on hemodialysis (n=28). Patients
were divided into 2 groups; pre-dialysis group (13) and post-dialysis group (15)
who received treatment before and after dialysis respectively. The patients were
given paritaprevir 75 mg/ ombitasvir 12.5 mg/ ritonavir 50 mg± ribavirin twice
per day for 12 weeks. The Ctrough concentratin was measured as a group PK
variability indicator. PD comparison was performed via clinical monitoring of
patients along with the quantitative assesment of the viral load.
Our results revealed that the sustained virologic response (SVR) was achieved in
both groups 27/28 (96.4%) patients. No significant difference between plasma
levels in both groups was observed (p=0.6725). An interindividual variation in
plasma level was observed among recruited subjects. This is especially important
due to the presence of ritonavir which is a potent CYP inhibitor. A variation in
its level will affect the plasma concentration of any concomitantly administered
drug. This mandates the TDM to avoid toxicity or treatment failure. In
conclusion, there is no need for specific dose scheduling for (paritaprevir /
ombitasvir / ritonavir) administered in HCV infected patients on hemodialysis
but TDM may be recommended to overcome interindividual variations.
References:
1. (a) Smolders, E. J.; de Kanter, C. T. M. M.; van Hoek, B.; Arends, J. E.; Drenth, J. P. H.;
Burger, D. M., Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in
Patients with Liver and/or Renal Impairment. Drug Safety 2016, 39 (7), 589-611; (b)
Stemer, G.; Lemmens-Gruber, R., Clinical pharmacy activities in chronic kidney disease
and end-stage renal disease patients: a systematic literature review. BMC
nephrology 2011, 12 (1), 35.

BOOK OF ABSTRACTS CHEM 08 (2020) Page 59