title: Pharmacokinetics and pharmacodynamics of famotidine and ranitidine in critically ill children.
abstract: To characterize and compare acid suppression (pharmacodynamics) and pharmacokinetics of IV famotidine and ranitidine in critically ill children at risk for stress gastritis. Single-blind, randomized study in PICU patients 6 months to 18 years requiring mechanical ventilation with continuous gastric pH monitoring, randomized to IV famotidine 12 mg/m(2) or ranitidine 60 mg/m(2) when gastric pH < 4.0 >1 hour with serial blood sampling following first dose. Twenty-four children randomized to either famotidine (n = 12) or ranitidine (n = 12). Sixteen out of twenty-four completed both PK and PD study arms (7/12 famotidine; 4.7 ± 3.4 years; 9/12 ranitidine; 6.6 ± 4.7 years; p = 0.38). Time to gastric pH 4.0 and total time pH above 4.0 similar with no difference in pH at 6 and 12 hours (p > 0.2). No difference between drugs in clearance, volume of distribution and half-life (p > 0.05). Ratio of AUC pH to AUC drug concentration 0-12 hours after first dose was significantly greater for famotidine (0.06849 ± 0.01460 SD) than ranitidine (0.02453 ± 0.01448; p < 0.001) demonstrating greater potency of famotidine. pH lowering efficacy of both drugs is similar. Greater potency of famotidine may offer clinical advantage due to lower drug exposure and less frequent dosing to achieve same pH lowering effect.
authors.affiliation: Division of Gastroenterology, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Shailender
authors.initials: S
authors.lastname: Madani
authors.forename: Ralph
authors.initials: R
authors.lastname: Kauffman
authors.forename: Pippa
authors.initials: P
authors.lastname: Simpson
authors.forename: Victoria Tutag
authors.initials: VT
authors.lastname: Lehr
authors.forename: Mary Lieh
authors.initials: ML
authors.lastname: Lai
authors.forename: Ashok
authors.initials: A
authors.lastname: Sarniak
authors.forename: Vasundhara
authors.initials: V
authors.lastname: Tolia
mesh_terms: D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D015738:Famotidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000737:chemistry / Q000378:metabolism; D005745:Gastric Acidity Determination; D005756:Gastritis / Q000188:drug therapy / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007223:Infant; D007262:Infusions, Intravenous; D011899:Ranitidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016037:Single-Blind Method
chemical_list: D006635:Histamine H2 Antagonists; D015738:Famotidine; D011899:Ranitidine
keywords: famotidine; gastric acid suppression; pediatric intensive care unit; pharmacodynamics; pharmacokinetics; ranitidine