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                                                                   EXHIBIT 10.1


                                   AMENDMENT


     This Amendment to Secured Promissory Note dated December 31, 1996 by
Connective Therapeutics, Inc. (now known as Connetics Corporation, the "Maker")
in favor of SmithKline Beecham Corporation ("Payee")(the "Note") is entered into
this 13th day of November, 1997. The parties hereto intending to be legally
bound hereby agree as follows:

     1. Section 2 of the Note is hereby amended in its entirety to read as
follows:

         Maker promises to make payments of principal under this Note on the
     following dates (each a "Payment Date"):

              April 1, 1998             $1,000,000
              October 1, 1998           $1,500,000
              January 4, 1999           $3,500,000
              January 7, 1999           $5,000,000

         On April 1, 1998 in addition to the payment of principal set forth
     above, the Maker shall pay interest on all principal amounts outstanding
     under the Note for the period from January 1, 1998 through March 31, 1998
     at the Interest Rate (as defined below), calculated on the basis of actual
     days and a 360-day year. On each subsequent Payment Date in addition to the
     payment of principal set forth above for such Payment Date, the Maker shall
     pay the Payee interest on all principal amounts outstanding under the Note
     for the period from the immediately prior Payment Date through the day
     preceding the current Payment Date calculated on the basis of actual days
     and a 360-day year. The "Interest Rate" shall be equal to sum of (a) the
     prime rate as publicly announced by Citibank NA from time to time plus 2%.

     2. The second sentence of Section 5 of the Note is amended in its entirety
to read as follows:

         Any prepayments shall be applied first to any accrued by unpaid
     interest and thereafter to reduce the next principal payment due.

     3. Any defined terms used herein and not otherwise defined in this
Agreement shall have the meanings set forth in the Note.

     IN WITNESS WHEREOF, the parties have duly caused this Amendment to be
executed as this 13th day of November, 1997.

                                   CONNETICS CORPORATION

                                   By: /s/ Thomas G. Wiggans
                                       -------------------------------------
                                       Thomas G. Wiggans
                                       President and Chief Executive Officer

                                   SMITHKLINE BEECHAM CORPORATION

                                   By: /s/ Donald F. Parman
                                       -------------------------------------
                                       Donald F. Parman
                                       Secretary



The undersigned hereby consent to the foregoing amendment to the terms of the
Note and acknowledges that such amendment shall not constitute a breach or event
of default under the terms of the Loan and Security Agreement dated as of July
18, 1995 or the Loan and Security Agreement dated as of December 21, 1995
between the Maker and each of Silicon Valley Bank and MMC/GATX Partnership No.
1.

Silicon Valley Bank                   MMC/GATX Partnership No. 1


By: ____________________________      By: _____________________________

Title: _________________________      Title: __________________________

Date: __________________________      Date: ___________________________