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EFFECT OF METHYLDOPA ON CREATININE

ESTIMATION

SIR,-Methyldopa is known to interfere with theestimation of creatinine. 1 It seemed possible that thiserror might be significant in clinical practice. We havetherefore investigated the extent of this interference.Creatinine was estimated by the method of Owen et awl. 2and also by AutoAnalyzer ’ (Technicon). The firstmethod uses fuller’s earth to adsorb creatinine in acidsolution, followed by elution with alkaline picrate, thusseparating the creatinine from interfering substances.The autoanalyzer dialyses samples into an air-segmentedwater stream which then mixes with an alkaline-picratestream. Known amounts of a-methyldopa were added tocreatinine standard solutions and the apparent creatinineconcentration was estimated by each of these two methods.Table I shows the result for the fuller’s-earth method.

TABLE I-EFFECT OF METHYLDOPA ON ESTIMATION OF CREATININE

BY FULLER’S EARTH

TABLE II-EFFECT OF METHYLDOPA ON ESTIMATION OF CREATININE

BY AUTOANALYZER

No error arises until the concentration of methyldopa israised to 2 mg. per ml. Table n shows the results given bythe autoanalyzer. There is a difference of approximately0-7 mg. per 100 ml. between the actual and the estimatedcreatinine concentration with methyldopa levels as low as0-25 mg. per ml. This error increases greatly with largeramounts of the drug.The work of Myhre et al. indicates that plasma levels

of methyldopa will rarely exceed 0-25 mg. per ml. We donot think any significant error will occur in the estimationof the creatinine concentration of plasma samples frompatients taking methyldopa. In our laboratory urine

samples are diluted 1 in 200 for the fuller’s-earth methodand 1 in 10 for the autoanalyzer. Because of this dilutionno error will occur in estimating the creatinine concentra-tion of urinary samples from patients taking methyldopaif the fuller’s-earth method is used. However, preliminarydata would suggest that an error may occasionally occurif the autoanalyzer is used. The estimated creatinineconcentration given by the autoanalyzer for six of fifteenurinary samples from 11 patients taking 0-5-2-0 g. per dayof methyldopa was 7-60 mg. per ml. greater than theresult from the fuller’s-earth method. The normal varia-

1. Young, J. A., Edwards, K. D. G. J. Pharmac. exp. Ther. 1964,145, 102.

2. Owen, J. A., Iggo, B., Scandrett, F. J., Stewart, C. P. Biochem. J.1954, 58, 426.

3. Myhre, E., Stenbaek, Ö., Brodwell, E. K., Hansen, T. Scand. J.clin. Lab. Invest. 1972, 29, 195.

tion between these methods is less than 3 mg. per 100 ml. 4

We therefore advise caution in interpreting changes inrenal function as indicated by the creatinine clearanceunder these circumstances.A recent issue of Clinical Chemistry 5 cites many examples

of drugs interfering with clinical laboratory tests. Wetherefore envisage that future request forms for chemical-pathology tests will require the clinician to list the drugsbeing taken by the patient.

K.R.U.F. Institute of Renal Disease,Welsh National School of Medicine,

Cardiff Royal Infirmary,Cardiff CF2 1SZ.

J. MADDOCKSS. HANNMARGARET HOPKINSG. A. COLES.

ANTIGEN/BIOLOGICAL-ACTIVITY RATIOFOR FACTOR VIII

SIR,-It was thought that classical haemophilia resultedfrom lack of synthesis of factor vni. However, it has nowbeen shown 6-8 that the plasma of severe hacmophilicpatients is able to react with a rabbit antibody to purifiedhuman factor vm, whereas in severe von Willebrand’sdisease there is no reaction. It thus appears that ha:mo-

philic patients produce a biologically inactive variant ofthe factor-vm molecule whilst in von Willebrand’s diseasethe factor-vm molecule is not synthesised. It has alsobeen found that factor-vm antigen is present in raised

4. Hudson, H., Rapoport, A. Clin. Chem. 1968, 14, 222.5. ibid. 1972, 18, 1041.6. Bennett, E., Huehns, E. R. Lancet, 1970, ii, 956.7. Zimmerman, T. S., Ratnoff, O. D., Powell, A. E. J. clin. Invest.

1971, 50, 244.8. Meyer, D., Lavergne, J.-M., Larrieu, M.-J., Josso, F. Thrombosis

Res. 1972, 1, 183.

Fig. 1-Biological and antigenic measurement of factor VIIIin 18 normal females (8) and 18 obligatory carriers of

haemophilia ( :: ).

Plotting the ratio antigen; biological activity v. biologicalactivity exploits the discrimination provided by both parameters.