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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.

Purpose Studies in animal models of acetaminophen (APAP) toxicity have reported the upregulation of cytokines, some of which are anti‐inflammatory or involved in hepatocyte regeneration. To further study this relationship, cytokines were measured in children/adolescents with acute APAP overdose. Methods: ELISA measurements of IL6, IL8, IL10, and MCP1 were performed on serum samples of APAP overdose patients. Results: 76 patients (age 13.72±4.41 yrs; 64 females) were enrolled and stratified by toxicity subgroups: Grp 1 (no/mild toxicity; AST<100 IU/L, n=51), Grp 2 (moderate toxicity; AST≥100 & ≥1000 IU/L, n=12), Grp 3 (severe toxicity, AST>1000 IU/L, n=13). A significant relationship was present for MCP1 (presented as median, range) (Grp 1, 628.0 pg/mL, 181.6‐1800.4; Grp 2, 1137.3 pg/mL, 167.8‐1808.1; Grp 3, 2777.1 pg/mL, 472.6‐6291.3) and toxicity subgroups (p<0.001). PT was higher (17.6 sec, 11.4‐43.8 vs. 14.1 sec, 10.6‐27.5; p<0.001) in patients with elevated MCP1 and in patients with delays in N‐acetylcysteine (p<0.0003). Grp 2+3 had higher values for IL6 (5.3 pg/mL, 0.0‐58.3, p=0.023) than Grp 1 (0.0 pg/mL, 0.0‐35.2) and higher values for IL8 (17.6 pg/mL, 0.0‐1013.8, p=0.027) than Grp 1 (0.0pg/mL, 0.0–1278.3). Conclusions: MCP1, a cytokine with hepatoprotective properties, appears to have a strong relationship with clinical measures of toxicity/risk in APAP overdose. This study supports the involvement of cytokines in repair processes in APAP toxicity. Clinical Pharmacology & Therapeutics (2004) 75, P50–P50; doi:

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