षढोः कः सि

Operational rule vidhi

षकार and ढकार not occurring at end of a पद are converted to ककार when followed by सकार.

Word by word (padaccheda)

Target षढोः ṣaṣṭhī · dvivacanaSubstitute / term कः prathamā · ekavacanaRight context सि saptamī · ekavacana

Target Ṣaṣṭhī (6th case): names what gets replaced, "in place of X" (1.1.49 षष्ठी स्थानेयोगा).
Substitute / term Prathamā (1st case): in operational rules, the substitute or the thing introduced; in definitions, the term or its referent.
Right context Saptamī (7th case): "when X follows", the operation applies to what precedes (1.1.66 तस्मिन्निति निर्दिष्टे पूर्वस्य). Also a condition or domain ("in the sense of").

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Full reading

षढोः कः सि

Pāṇini leaves out words that carry over from earlier sūtras. Expand to see the rule as a reader actually understands it.

As a rewrite rule (sketch from case endings)

षढोः → कः / सि

Replace ṣaḍhoḥ with kaḥ when si follows. Inherited words (anuvṛtti) may add further conditions.

Commentary

क is substituted for ष or ढ before स।
Thus for ष of विष् we have विवेक्ष्यते, अवेक्ष्यत्, विविक्षति ॥ For ढ of लिड् (लिढ 8.2.31) we have लेक्ष्यति, अलेक्ष्यत्, लिलिक्षति ॥

For the स of the affix स्य &c, is substituted ष by 8.3.59.

Why do we say "before स"? Observe पिनष्टि, लेढि ॥

Śrīśa Chandra Vasu, The Ashtadhyayi of Panini (1897), via ashtadhyayi.com.