Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers

Citation:
Kassem, M. A., A. Ali, S. Farid, and M. Al-Ghobashy, "Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers", Clinical Drug Investigation, vol. 36, issue 2, pp. 147–155, 2016.

Abstract:

Abstract
Objective Midodrine is an a-agonist prodrug of desglymidodrine
used for the management of hypotension, and
can also be used for hepatorenal syndrome and cirrhotic
patients with tense ascites. The objective of the present
work was to study the clinical pharmacokinetic parameters
of midodrine and its active metabolite desglymidodrine in
cirrhotic patients with tense ascites, which may help in
dose selection and improve treatment outcome.
Method This was a prospective, open-label, single-dose,
parallel-group study. At first, a pilot study was performed on
one healthy volunteer by taking serial blood samples at
scheduled time intervals to validate the method of analysis
and sampling times. The full study was then conducted by
selecting 12 cirrhotic patients with tense ascites in one group
and taking nine blood samples. We also selected five healthy
volunteers as the control group and took 11 blood samples.
Results Statistically significant differences were observed
between the healthy volunteer group and the patients group
in the area under the concentration versus time curve
(AUC0–t) and maximum plasma concentration (Cmax) values
of midodrine and desglymidodrine. Based on the
results of the pharmacokinetic analysis, the patient group
was further subdivided into those receiving the interacting
drug ranitidine (five patients) and those not receiving the
interacting drug (seven patients).
Conclusions Pharmacokinetic parameters of midodrine
can differ significantly in cirrhotic patients with tense
ascites from those in healthy individuals. Drug monitoring,
dose adjustments, and drug–drug interactions should all be
considered during therapy in this vulnerable patient group.