Effect of Certain Physical Factors on the In Vitro Testing of Anthelmintics. ∗

Abstract

Although certain investigators have done much to destroy confidence in the value of in vitro methods of testing anthelmintics by drawing too sweeping conclusions from uncontrolled experiments, these methods are of value and were used successfully by Lamson et al. 1 in their studies on the alkyl resorcinols. These studies have resulted in the establishment of hexyl resorcinol as an effective as-caricide of relatively low toxicity. This method of in vitro testing of ascaricides is described elsewhere, 2 but there remains for discussion certain physical factors which must be guarded against if reliable results are to be obtained.

As Lo Monaco 3 has already shown with santonin, an undissolved excess of the drug must be present in the testing solution for the best results, but he makes no mention of the effect of the physical state of the excess. However, a solid excess is far less effective than a liquid excess as will be shown. If certain substances, such as heptyl resorcinol, are allowed to stand for sometime in contact with 1,000 parts of 0.9% NaCl solution at 37° C, a part of the chemical will be dissolved, but as these substances are less soluble than 1 to 1,000 a solid excess will remain. If another sample of this same chemical is heated in contact with the same relative amount of 0.9% NaCl and cooled to 37° C. we shall have 2 mixtures of the drug and saline with the sole difference that in one instance the undissolved excess is a solid, while in the other it is a supercooled liquid. When these 2 mixtures are tested against Ascaris lumbricoides of swine, it is found that the one with liquid excess will kill the worms in a much shorter time. Table I records the results obtained when several of these substances were tested with both a solid and a liquid excess.