the harp seal, Pagophilus groenland- icus, the hooded seal, Cystophora cris- tata, the harbour seal, Phoca vitulina and the grey seal, Halichoerus grypus,.
CORRESPONDENCE
Drug bioavailability To the editor: Since its formation in June 1974 the permanent health protection branch (HPB) advisory committee on drug bioavailability (see Can Med Assoc J 109: 920, 1973) has reviewed the protocols of all bioavailability studies carried out or sponsored by the HPB. The committee has evaluated the results of those studies and made recommendations to the HPB. The purpose of the present communication is to acquaint members of the health professions with some of these recommendations and the subsequent actions the HPB has taken. The committee has continued to examine data on digoxin products on the Canadian market as a consequence of actions taken in 1973 resulting in withdrawal of certain products. This information was communicated to the health professions in December 1973. The HPB is exercising careful and continuing surveillance over the manufacture and quality control of digoxin products, with emphasis on the consistent bioavailability of available products. Protocols for assessment of the bioavailability of diphenylhydantoin (phenytoin) dosage forms were reviewed by the committee, as were the resulting data when the HPB study was completed. All products were of satisfactory bioavailability; details of the full study will be published soon in the scientific literature. The committee has evaluated the data resulting from a bioavailability study of phenylbutazone (100 mg) products. The data showed that there were considerable differences between products in the total amount of phenylbutazone absorbed as well as in the rate at which the drug was absorbed. Contributions to the Correspondence section are welcomed and if considered suitable will be published as space permits. They should be typewritten double spaced and should not exceed 1½ pages in length.
Since the range of concentrations required for therapeutic effects or associated with toxic effects is ill defined, the committee recommended that all products be considered of satisfactory bioavailability if the area under the time-serum concentration curve (AUC) for the product was between 80 and 125% of that of the reference product, which was assigned a value of 100%. As a result of this recommendation several products were withdrawn from the market. The committee has evaluated data on the bioavailability of the following four oral (10 mg) warfarin products: * Coumadin (Endo, sodium salt, lot no. EL 681 C). * Warfilone (Frosst, sodium salt, lot no. 1295 T); the 10-mg strength was subsequently discontinued by the manufacturer. *Warnerin (Warner/Chilcott, sodium salt, lot no. 004062). * Athrombin-K (Purdue Frederick, potassium salt, lot no. AU75). Results showed that the AUC for the products ranged from 87 to 101% of that of the reference product, which was assigned a value of 100%. There were considerable differences in the observed maximum serum concentrations (78 to 100% of that of the reference product) and in the time taken to reach this maximum concentration (means, 1.8 to 3.7 hours). The significance of these differences is not known. However, because small differences in warfarin dosage can cause large alterations in prothrombin content, particularly at the therapeutic dose, the committee recommended that except in emergencies it was unwise, if not unsafe, to substitute or interchange one product for another without taking all the precautions ordinarily taken when oral anticoagulant therapy is first begun. Since the dosage of warfarin should always initially be carefully adjusted to achieve a safe and effective
level of anticoagulation, the committee recommended that all products be considered to have satisfactory, though different, bioavailability characteristics. It is anticipated that a study of quinidine products sold in Canada will begin soon since satisfactory methodology is available. A complete protocol for such an investigation has been approved by the committee. Some of the information referred to above has been published in QUAD reviews, which can be obtained from the HPB. J. RUEDY, MD, FRCP[C] chairman R.O. DAVIES, MD, PH D MA. GAGNON, MD, D SC
W.M. MCLEAN, PHARM D T.G. Virri, PH D
W.G. THOMPSON, MD, FRCP[C]
T.W. WILSON, MD, M SC, FRCP[Ci Advisory committee on drug bioavailability Health protection branch Health and Welfare Canada Ottawa, ON
Seal finger: an unsolved medical problem in Canada To the editor: Seal finger, or Spekkfinger, as it is known in Norway, is an infection caused by an as yet unidentified organism carried in the blood or fat of seals. In Canada there remains a significant number of people who derive a large part of their income from seal hunting. The Canadian Inuit, almost all of whom are coastal dwellers, continue to depend on the ringed seal, Phoca hispida, as the basis of their economy. They also hunt the bearded seal, Erignathus barbatus, and the walrus, Odobenus rosmarus. Many Newfoundianders and other maritimers hunt the harp seal, Pagophilus groenlandicus, the hooded seal, Cystophora cristata, the harbour seal, Phoca vitulina and the grey seal, Halichoerus gry pus, for their pelts. Candolin, in a comprehensive study of the many regions of the gulfs of
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