A pharmacokinetic approach based on creatinine clearance has been outlined which permits drug dosage regimen adjustments in patients with renal impairment. The parameters needed for calculating a loading dose and a maintenance regimen are the fraction of a dose excreted unchanged in the urine, the creatinine clearance of the patient, and the half-life of the drug in patients with normal renal function. In varying degrees of renal failure, predicted dosage regimens agree closely with dosage regimens predicted by other methods for a number of drugs.
OrmeB. M., and CutlerR. E.: The Relationship Between Kanamycin Pharmacokinetics: Distribution and Renal Function, Clin. Pharmacol. Ther.10: 543–550 (July-Aug.) 1969.
2.
CutlerR. E.: Correlation of Serum Creatinine Concentration and Gentamicin Half-Life, J. Amer. Med. Assoc.219: 1037–1041 (Feb. 21) 1972.
3.
ChanR. A.: Gentamicin Therapy in Renal Failure: a Nomogram for Dosage, Ann. Intern. Med.76: 773–778 (May) 1972.
4.
JelliffeR. W.: An Improved Method of Digoxin Therapy, Ann. Intern. Med.69: 703–717 (Oct.) 1968.
5.
JelliffeR. W.: An Improved Method of Digitoxin Therapy, Ann. Intern. Med.72: 453–464 (Apr.) 1970.
6.
DettliL.: Multiple Dose Kinetics and Drug Dosage in Patients with Kidney Disease, Acta. Pharmacol.29 (Suppl. 3): 211–224, 1971.
7.
WagnerJ. G.: Biopharmaceutics and Relevant Pharmacokinetics. 1st ed. Drug Intelligence Publications, Hamilton, Il. 62341, 1971, p. 222–233.
8.
Koch-WeserJ.: Drug therapy. Serum Drug Concentrations as Therapeutic Guides, N. Eng. J. Med.287: 227–231 (Aug. 3) 1972.
9.
VessellE. S., and PassanantiG. T.: Utility of Clinical Chemical Determinations of Drug Concentrations in Biological Fluids, Clin. Chem.17: 851–865 (Sept.) 1971.
10.
WagnerJ. G.: Blood Levels of Drug at the Equilibrium State After Multiple Dosing, Nature207: 1301–1302, 1965.
11.
Kruger-ThiemerE.: Continuous Intravenous Infusion and Multicompartment Accumulation, Eur. J. Pharmacol.4: 317–324, 1968.
12.
Van RossumJ. M., and TomeyA.H.J.M.: Multicompartment Kinetics and the Accumulation Plateau, Arch. Int. Pharmacodyn.188: 200–203, 1970.
13.
BoxerG. E.: Streptomycin in the Blood: Chemical Determinations After Single and Repeated Intramuscular Injections, J. Pharmacol. Exp. Ther.92: 226–235, 1948.
14.
Kruger-ThiemerE.: Dosage Schedule and Pharmacokinetics in Chemotherapy, J. Amer. Pharm. Assoc., Sci. Edit.49: 311–313, 1960.
15.
HirschmanJ. L., and BorgsdorfL. R.: The DIAS Rounds. Drug Intell. Clin. Pharm.5: 251 (Aug.) 1971.
16.
RitschelW. A.: Biological Half-Lives and Their Clinical Applications, in Perspectives in Clinical Pharmacy. 1st. ed. FranckeD. E., and WhitneyH. A. K.Jr., editors, Drug Intelligence Publications.Hamilton, Il. 62341, 1972, p. 286–324.
17.
WeinsteinL.: Antibiotics, in The Pharmacological Basis of Therapeutics. 4th ed. GoodmanL. S., and GilmanA., editors, the Macmillan Co. New York, New York, 1970, p. 1269–1310.
18.
GingellJ. C., and WaterworthP. M.: Dose of Gentamicin in Patients With Normal Renal Function and Renal Impairment, Brit. Med. J.2: 19–22 (Apr. 6) 1968.
19.
LevyG.: Dose Dependent Effects in Pharmacokinetics, in Importance of Fundamental Principles in Drug Evaluation, TedeschiD. H., and TedeschiR. E., editors, Raven Press, New York, New York, 1968. p. 141–172.
20.
LevyG.: Limited Capacity for Salicylate Elimination in Man, Clin. Pharmacol. Ther.13: 258–268 (Mar.-Apr.) 1972.
21.
BrodieB. B., and HogbenC. A. M.: Some Physico-Chemical Factors in Drug Action, J. Pharm. Pharmacol.9: 345–380, 1957.
GibaldiM., and PerrierD.: Drug Elimination and Apparent Volume of Distribution in Multicompartment Systems, J. Pharm. Sci.61: 952–953 (June) 1972.
24.
JuskoW. J., and GibaldiM.: Effects of Change in Elimination on Various Parameters of the Two-Compartment Open Model, J. Pharm. Sci.61: 1270–1273 (Aug.) 1972.
25.
GibaldiM., and PerrierD.: Drug Distribution and Renal Failure, J. Clin. Pharmacol.12: 201–204 (May-June) 1972.
26.
ShoemanD. W., and AzarnoffD. L.: The Alteration of Plasma Proteins in Uremia as Reflected in Their Ability to Bind Digitoxin and Diphenylhydantoin, Pharmacology7: 169–177, 1972.
27.
ReidenbergM. M.: Protein Binding of Diphenylhydantoin and Desmethylimipramine in Plasma From Patients With Poor Renal Function, N. Eng. J. Med.285: 264–267 (July 29) 1971.
28.
FischerE.: Renal Excretion of Sulfadimidine in Normal and Uremic Subjects, Lancet2: 210–212 (July 29) 1972.
29.
LevyG., and JuskoW. J.: Factors Affecting the Absorption of Riboflavin in Man, J. Pharm. Sci.55: 285–289 (Mar.) 1966.
30.
MayersohnM.: Ascorbic Acid Absorption in Man — Pharmacokinetic Implications, Eur. J. Pharmacol.19: 140–142, 1972.
31.
BorgstromB.: Lymphatic Transport of Cholesterol in Human Beings. Effect of Dietary Cholesterol. Scand. J. Clin. Lab. Invest.26: 227–235, 1970.