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March 1, 1985, Vol 253, No. 9 >
ARTICLE | March 1, 1985

Increased Cimetidine Clearance in Burn Patients FREE

J. A. Jeevendra Martyn, MD; David J. Greenblatt, MD; Darrell R. Abernethy, MD, PhD
[+] Author Affiliations

Reprint requests to Department of Anesthesiology, Massachusetts General Hospital, Boston, MA 02114 (Dr Martyn).


JAMA. 1985;253(9):1288-1291. doi:10.1001/jama.1985.03350330086028
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References

To determine the etiology of the decreased efficacy of cimetidine in burned and critically ill surgical patients, we studied the kinetics and dynamics of the drug in eight burned patients at a mean of 12 days after the burn. The kinetics were compared with those of nine healthy controls. The elimination half-life of cimetidine in burned patients was significantly reduced (2.2 v 1.5 hours), and total clearance significantly increased (8.2 v 13.3 mL/min/kg). Creatinine and total cimetidine clearance were highly correlated with size of the burn. In the patients studied, 63% of the dose was excreted in eight hours, compared with 45% after 24 hours in controls. Gastric pH was maintained at 4 or higher as long as plasma levels of cimetidine were held above 0.5 μg/mL. Thus, the increased clearance of cimetidine might explain the decreased effectiveness of this drug in burned and possibly other surgical patients. Dose schedules may need to be altered to compensate for the enhanced clearance of this drug.

(JAMA 1985;253:1288-1291)

REFERENCES

1 +
Gump FE, Price JB, Kinney JM:  Whole body and splanchnic blood flow and oxygen consumption measurements in patients with intraperitoneal infection . Ann Surg 1970;;171:321-328.
2 +
Wilmore DW, Goodwin CW, Aulick LH, et al:  Effect of injury and infection on visceral metabolism and circulation . Ann Surg 1980;; 192:491-504.
3 +
Martyn JAJ, Greenblatt DJ, Quinby WC:  Diazepam kinetics in patients with severe burns . Anesth Analg 1983;;62:293-297.
4 +
Priebe HJ, Skillman JJ, Bushnell LS, et al:  Antacid versus cimetidine in preventing acute gastrointestinal bleeding: A randomized trial in 75 critically ill patients . N Engl J Med 1980;; 302:426-430.
5 +
Isenberg JI, Peterson WL, Elashoff JD, et al:  Healing of benign gastric ulcer with low dose antacid or cimetidine: A double blind, randomized, placebo-controlled trial . N Engl J Med 1983;;308:1319-1324.
6 +
Finkelstein W, Isselbacher KJ:  Cimetidine . N Engl J Med 1978;;299:992-996.
7 +
Weigelt JA, Aurbakken CM, Gewertz BL, et al:  Cimetidine v antacid prophylaxis for stress ulceration . Arch Surg 1981;;116:597-601.
8 +
Martyn JAJ:  Cimetidine and/or antacid for the control of gastric acidity in pediatric burn patients . Crit Care Med 1985;;13:1-3.
9 +
Goudsouzian NG, Coté CJ, Liu LMP, et al:  The dose-response effects of oral cimetidine on gastric pH and volume in children . Anesthesiology 1981;;55:533-536.
10 +
Lorenzo B, Drayer DE:  Improved method for the measurement of cimetidine in human serum by reverse phase high-pressure liquid chromatography . J Lab Clin Med 1981;;97:545-550.
11 +
Greenblatt DJ, Pfeifer HJ, Ochs H, et al:  Pharmacokinetics of quinidine in humans after intravenous, intramuscular and oral administration . J Pharmacol Exp Ther 1977;;202:365-378.
12 +
Burland WL, Duncan WAM, Hesselbo T, et al:  Pharmacological evaluation of cimetidine, a new H2-receptor antagonist in healthy man . Br J Clin Pharmacol 1975;;2:481-486.
13 +
Pancorbo S, Bubrick MP, Chin TWF, et al:  Cimetidine dynamics after repeated intravenous injection . Clin Pharmacol Ther 1984;;35:50-54.
14 +
Cullen DJ:  Results and costs of intensive care . Anesthesiology 1977;;47:203-216.
15 +
Kohler TR, Dellinger EP, Simonwitz DA, et al:  Cimetidine pharmacokinetics in trauma patients . Surg Forum 1979;;30:12-14.
16 +
Martyn JAJ, Liu LMP, Szyfelbein SK, et al:  The neuromuscular effects of pancuronium in burned children . Anesthesiology 1983;;59:561-564.
17 +
Sawchuk RJ, Rector TS:  Drug kinetics in burn patients . Clin Pharmacokinetics 1980;;5:548-556.
18 +
Ziemniak JA, Watson WR, Saffle JR, et al:  Cimetidine kinetics during resuscitation from burn shock , abstracted. Clin Pharmacol Ther 1984;;36:228-233.
19 +
Martyn JAJ, Snider MT, Szyfelbein SK, et al:  Right ventricular dysfunction in acute thermal injury . Ann Surg 1980;;191:330-335.
20 +
McElwee HP, Sirinek KR, Levine BA:  Cimetidine affords protection equal to antacids in the prevention of stress ulceration following burns . Surgery 1979;;86:620-626.
21 +
Williams RL:  Drug administration in hepatic disease . N Engl J Med 1983;;309:1616-1622.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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1 +
Gump FE, Price JB, Kinney JM:  Whole body and splanchnic blood flow and oxygen consumption measurements in patients with intraperitoneal infection . Ann Surg 1970;;171:321-328.
2 +
Wilmore DW, Goodwin CW, Aulick LH, et al:  Effect of injury and infection on visceral metabolism and circulation . Ann Surg 1980;; 192:491-504.
3 +
Martyn JAJ, Greenblatt DJ, Quinby WC:  Diazepam kinetics in patients with severe burns . Anesth Analg 1983;;62:293-297.
4 +
Priebe HJ, Skillman JJ, Bushnell LS, et al:  Antacid versus cimetidine in preventing acute gastrointestinal bleeding: A randomized trial in 75 critically ill patients . N Engl J Med 1980;; 302:426-430.
5 +
Isenberg JI, Peterson WL, Elashoff JD, et al:  Healing of benign gastric ulcer with low dose antacid or cimetidine: A double blind, randomized, placebo-controlled trial . N Engl J Med 1983;;308:1319-1324.
6 +
Finkelstein W, Isselbacher KJ:  Cimetidine . N Engl J Med 1978;;299:992-996.
7 +
Weigelt JA, Aurbakken CM, Gewertz BL, et al:  Cimetidine v antacid prophylaxis for stress ulceration . Arch Surg 1981;;116:597-601.
8 +
Martyn JAJ:  Cimetidine and/or antacid for the control of gastric acidity in pediatric burn patients . Crit Care Med 1985;;13:1-3.
9 +
Goudsouzian NG, Coté CJ, Liu LMP, et al:  The dose-response effects of oral cimetidine on gastric pH and volume in children . Anesthesiology 1981;;55:533-536.
10 +
Lorenzo B, Drayer DE:  Improved method for the measurement of cimetidine in human serum by reverse phase high-pressure liquid chromatography . J Lab Clin Med 1981;;97:545-550.
11 +
Greenblatt DJ, Pfeifer HJ, Ochs H, et al:  Pharmacokinetics of quinidine in humans after intravenous, intramuscular and oral administration . J Pharmacol Exp Ther 1977;;202:365-378.
12 +
Burland WL, Duncan WAM, Hesselbo T, et al:  Pharmacological evaluation of cimetidine, a new H2-receptor antagonist in healthy man . Br J Clin Pharmacol 1975;;2:481-486.
13 +
Pancorbo S, Bubrick MP, Chin TWF, et al:  Cimetidine dynamics after repeated intravenous injection . Clin Pharmacol Ther 1984;;35:50-54.
14 +
Cullen DJ:  Results and costs of intensive care . Anesthesiology 1977;;47:203-216.
15 +
Kohler TR, Dellinger EP, Simonwitz DA, et al:  Cimetidine pharmacokinetics in trauma patients . Surg Forum 1979;;30:12-14.
16 +
Martyn JAJ, Liu LMP, Szyfelbein SK, et al:  The neuromuscular effects of pancuronium in burned children . Anesthesiology 1983;;59:561-564.
17 +
Sawchuk RJ, Rector TS:  Drug kinetics in burn patients . Clin Pharmacokinetics 1980;;5:548-556.
18 +
Ziemniak JA, Watson WR, Saffle JR, et al:  Cimetidine kinetics during resuscitation from burn shock , abstracted. Clin Pharmacol Ther 1984;;36:228-233.
19 +
Martyn JAJ, Snider MT, Szyfelbein SK, et al:  Right ventricular dysfunction in acute thermal injury . Ann Surg 1980;;191:330-335.
20 +
McElwee HP, Sirinek KR, Levine BA:  Cimetidine affords protection equal to antacids in the prevention of stress ulceration following burns . Surgery 1979;;86:620-626.
21 +
Williams RL:  Drug administration in hepatic disease . N Engl J Med 1983;;309:1616-1622.

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