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                                                                 Exhibit 10.42.2

                                       January 28, 2004

BY FACSIMILE AND EXPRESS MAIL
CONFIDENTIAL
Peter A. Lankau
President
Endo Pharmaceuticals Inc.
100 Painters Drive
Chadds Ford, PA  19317

    Re: Amendment to Development, Commercialization and Supply License Agreement

Dear Peter:

Reference is made to the Development, Commercialization and Supply License
Agreement between Endo Pharmaceuticals Inc. ("Endo") and DURECT Corporation
("DURECT") effective November 8, 2002 ("Agreement"). Effective on the date
written above, Endo and DURECT hereby agree as follows:

         1.       Amendment to Section 4.6(a). Section 4.6(a) of the Agreement
                  shall be amended to change "June 30, 2004" to "January 1,
                  2005".

         2.       Restatement of Section 4.6(c). Section 4.6(c) of the Agreement
                  shall be deleted in its entirety, and in lieu thereof, the
                  following shall be inserted:

                  "(c) Notwithstanding anything to the contrary in Sections
                  4.6(a) and (b) and except as set forth in this Section 4.6(c),
                  Endo shall have no obligations under Sections 4.6(a) and (b)
                  to make any payments to DURECT for any Developments Costs
                  incurred up to and including the date on which the first
                  patient is dosed with the Product in the first clinical trial
                  of at least that number of patients necessary to satisfy the
                  FDA which occurs after the Effective Date (such date, the
                  "Trial Commencement Date" and such trial, the "First Trial").
                  Notwithstanding the foregoing: (i) in the event the Trial
                  Commencement Date has not occurred by December 31, 2003, then
                  during the period commencing on January 1, 2004 until the
                  earlier of the Trial Commencement Date or January 1, 2005,
                  Endo shall be responsible for 25% of the Development Costs
                  incurred in each such calendar month, up to an aggregate
                  payment by Endo to DURECT of $250,000 of Development Costs for
                  such period; and (ii) in the event the

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                  Trial Commencement Date has not occurred on or before January
                  1, 2005, then Endo shall be responsible for such portion of
                  the Development Costs incurred after January 1, 2005 in
                  accordance with Section 4.6(a). Furthermore, until the Trial
                  Commencement Date, DURECT hereby agrees to initiate any human
                  trial only if such trial and the initiation thereof is
                  consistent with a reasonable pharmaceutical company's overall
                  global strategic development plan for a product similarly
                  situated to the Product. Finally, in no event shall Endo be
                  liable for any costs associated with any human pharmacokinetic
                  (PK) study undertaken by DURECT prior to the earlier of the
                  Trial Commencement Date or January 1, 2005."

         3.       Restatement of Section 13.3(d). Section 13.3(d) of the
                  Agreement shall be deleted in its entirety, and in lieu
                  thereof, the following shall be inserted:

                  "(d) [INTENTIONALLY OMITTED.]"

         4.       Restatement of Section 13.3(e). Section 13.3(e) of the
                  Agreement shall be deleted in its entirety, and in lieu
                  thereof, the following shall be inserted:

                  "(e) In the event that the Trial Commencement Date shall not
                  have occurred on or before January 1, 2005, Endo shall have
                  the right to terminate this Agreement effective upon 10 days'
                  written notice with no further rights or obligations hereunder
                  (other than those rights or obligations which are expressly
                  indicated herein to survive termination or expiration of this
                  Agreement); provided that such written notice is delivered to
                  DURECT no later than January 31, 2005."

         5.       New Section 4.10. A new Section 4.10 shall be added to the
                  Agreement as follows:

                  "4.10 Retention of Key Personnel. DURECT shall use its
                  reasonable efforts to retain key personnel involved with the
                  development of the Product. Such key personnel shall be those
                  individuals identified as such by the JEC. In the event that a
                  member of the key personnel leaves the employ of DURECT
                  (either on his/her own volition or otherwise), DURECT shall,
                  within three (3) business days of such departure, inform

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                  Endo of (1) such fact and (2) DURECT's plan as to how it
                  intends to address the departure of such key personnel to
                  ensure the smooth continuance of the Development Program."

Except as set forth above, all other terms of the Agreement shall remain the
same. Please sign below to indicate Endo's agreement to the foregoing.

                                                     Very truly yours,

                                                     /s/ JAMES E. BROWN

                                                     James E. Brown
                                                     President and CEO

AGREED TO BY ENDO:

By: /s/ PETER A. LANKAU
    ----------------------
         Peter A. Lankau
         President

Date: January 28, 2004