title: Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers.
abstract: OBJECTIVE
  Midodrine is an α-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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pharmaceutics, Egyptian Russian University, Badr City, Egypt. ahmedclinicalbcps@yahoo.com.|, Qualiobia, Shebeen-Elquanater, Kafr Taha, Egypt. ahmedclinicalbcps@yahoo.com.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Clinical Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Samar
authors.initials: S
authors.lastname: Farid
authors.affiliation: Department of Internal Medicine, Cairo University, Cairo, Egypt.
authors.forename: Mona
authors.initials: M
authors.lastname: Amin
authors.affiliation: Department of Pharmaceutics, Cairo University, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kassem
authors.affiliation: Department of Internal Medicine, Cairo University, Cairo, Egypt.
authors.forename: Nouman
authors.initials: N
authors.lastname: Al-Garem
authors.affiliation: Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.|Bioanalysis Research Group, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Medhat
authors.initials: M
authors.lastname: Al-Ghobashy
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics*; D000328:Adult; D001201:Ascites / Q000188:drug therapy*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008879:Midodrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010865:Pilot Projects; D011355:Prodrugs / Q000493:pharmacokinetics*; D011446:Prospective Studies
chemical_list: D000316:Adrenergic alpha-Agonists; D011355:Prodrugs; D008879:Midodrine; C551228:desglymidodrine