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                                                                  EXHIBIT 10.18

                              SECOND AMENDMENT TO
                              EMPLOYMENT AGREEMENT

         This Second Amendment to Employment Agreement (the "Second Amendment")
is executed and dated effective as of the 29th day of October, 2002 between
Zonagen, Inc. (the "Company") and Louis Ploth, Jr. (the "Executive").

         WHEREAS, the Company and Executive entered into an Employment Agreement
dated as of October 16, 1993, as amended by the First Amendment to Employment
Agreement dated January 31, 2001 (as amended, the "Employment Agreement") which
Employment Agreement has been renewed pursuant to the terms thereof;

         WHEREAS, the Company and Executive now wish to amend certain provisions
of the Employment Agreement;

         NOW THEREFORE, in consideration of the foregoing and the mutual
covenants herein, the parties hereto agree as follows:

         1. Capitalized terms used but not defined herein have the respective
meanings set forth in the Employment Agreement.

         2. Section 3 of the Employment Agreement is hereby amended by deleting
subparagraph (ii) in its entirety.

         3. Section 6(g) of the Employment Agreement is hereby amended to
replace the first paragraph in its entirety with the following:

            "Notwithstanding anything in this Section 6 to the contrary,
            upon a Change of Control (as defined below), provided the
            Executive is an employee of the Company immediately prior
            thereto, the Company shall:

               (i) pay to the Executive, upon the closing of the Change of
                   Control, a lump sum cash payment equal to 1 times the
                   Executive's then current annual salary; such payment shall be
                   in lieu of any other payments payable to the Executive
                   pursuant to Section 6(a) above, and the terms of Sections
                   6(d) and 6(f) shall not apply in such instance;

               (ii) accelerate in full the vesting of all shares subject to any
                    of the Executive's outstanding stock options, and Executive
                    shall have a period of two years following the Change of
                    Control to exercise such options; and

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               (iii) continue, for the period of twelve (12) months commencing
                     on the date of such Change of Control, to provide the
                     benefits contemplated by Section 4(a) of this Agreement
                     (provided that the continuation of such benefits shall be
                     construed so as not to extend the period during which the
                     Company shall be required to provide benefits under COBRA
                     following the date of such Change of Control).

         4. Except as amended and modified by this Second Amendment, the
Employment Agreement shall continue in full force and effect. The Employment
Agreement and this Second Amendment shall be construed as one and the same
instrument.

         5. This Second Amendment may be signed in any number of counterparts,
each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument, and it shall not be necessary in making
proof of this Second Amendment to produce or account for more than one such
counterpart.

         6. This Second Amendment (i) constitutes the entire contract between
the parties relative to the amendments to the Employment Agreement made hereby,
(ii) supersedes all prior agreements, consents and undertakings relating to such
amendments and (iii) may not be contradicted by evidence of prior
contemporaneous or subsequent oral agreements of the parties.

         7. This Second Amendment shall be construed and enforced in accordance
with the laws of the State of Texas.

         8. This Second Amendment shall be binding upon and shall inure to the
benefit of and enforceable by the parties hereto and their respective successors
and assigns.


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         IN WITNESS WHEREOF, the parties have executed this Second Amendment to
the Employment Agreement effective (the "Effective Date") for all purposes as of
the date first above written.



EMPLOYEE                                      COMPANY

                                              ZONAGEN, INC.



/s/ Louis Ploth, Jr.                          By:  /s/ Joseph S. Podolski
--------------------------                         ----------------------------
Louis Ploth, Jr.                                   Joseph S. Podolski
                                                   President and
                                                   Chief Executive Officer


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