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                                                                   EXHIBIT 10.21


                                                                  EXECUTION COPY


                                            FIRST AMENDMENT dated as of November
                                    25, 1998 (this "FIRST AMENDMENT") to the
                                    Amended and Restated Credit Agreement dated
                                    as of February 26, 1998 (as amended,
                                    modified or otherwise supplemented through
                                    the date hereof, the "CREDIT AGREEMENT"),
                                    among Kendle International Inc. (the
                                    "BORROWER"), the Lenders (as defined in the
                                    Credit Agreement) and NationsBank, N.A., as
                                    Agent for the Lenders (in such capacity, the
                                    "AGENT"), and as Issuing Lender.

         Capitalized terms used and not otherwise defined herein shall have the
meanings assigned to such terms in the Credit Agreement (the Credit Agreement,
as amended by, and together with, this First Amendment, and as hereinafter
amended, modified, supplemented, extended or restated from time to time, being
called the "AMENDED CREDIT AGREEMENT").

         The Borrower has requested the Lenders to, among other things, amend
certain covenants contained in the Credit Agreement.

         The parties hereto have agreed, subject to the terms and conditions
hereof, to amend the Credit Agreement as provided herein.

         Accordingly, the parties hereto hereby agree as follows:

         SECTION 1. AMENDMENTS TO THE CREDIT AGREEMENT. Subject to satisfaction
of the conditions precedent set forth in Section 3 of this First Amendment, the
Credit Agreement is hereby amended as follows:

                  (a)      The definition of "Change of Control" contained in
         Section 1.1 of the Credit Agreement is hereby deleted therefrom in its
         entirety and the following definition is substituted in lieu thereof:

                  ""CHANGE OF CONTROL" shall mean any of the following events:
                  (a) any person or "group" (within the meaning of Rule 13d-5
                  under the Exchange Act), together with its Affiliates, other
                  than Candace Kendle Bryan and Christopher C. Bergen, shall
                  beneficially own, directly or indirectly, the lesser of (i) an
                  amount of Capital Stock of the Borrower entitled to twenty
                  percent (20%) or more of the Total Voting Power of the
                  Borrower or (ii) an amount of Capital Stock of the Borrower
                  entitled to a percentage of the Total Voting Power of the
                  Borrower in excess of the aggregate of such Capital Stock
                  owned, directly or indirectly, by Candace Kendle Bryan and
                  Christopher C. Bergen; (b) Candace Kendle Bryan and
                  Christopher C. Bergen together cease to own shares of Capital
                  Stock of the Borrower representing at least ten percent (10%)
                  of the Total Voting Power of the Borrower; or (c) during any
                  period of two consecutive years, individuals who at the
                  beginning of such period constituted the Board of Directors of
                  the Borrower (together with any new directors whose election
                  by such Board of Directors or whose nomination for election by
                  the shareholders of the Borrower was approved by a vote of
                  sixty-six and 2/3 percent


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                  (66-2/3%) of the directors of the Borrower then still in
                  office who were either directors at the beginning of such
                  period or whose election or nomination for election was
                  previously so approved) cease for any reason to constitute a
                  majority of the Board of Directors of the Borrower then in
                  office."

                  (b)      The definition of "Collateral Documents" contained in
         Section 1.1 of the Credit Agreement is hereby deleted therefrom in its
         entirety and the following definition is hereby substituted in lieu
         thereof:

                  ""COLLATERAL DOCUMENTS" shall mean the Pledge Agreement, the
                  Permitted Tax Distribution Agreements, such other documents
                  executed and delivered in connection with the attachment and
                  perfection of the Agent's security interests and liens arising
                  thereunder and all documents and instruments delivered under
                  and pursuant to Section 6.11."

                  (c)      The definition of "Fixed Charge Coverage Ratio"
         contained in Section 1.1 of the Credit Agreement is hereby deleted
         therefrom in its entirety and the following definition is hereby
         substituted in lieu thereof:

                  ""FIXED CHARGE COVERAGE RATIO" shall mean, as of any reporting
                  day, the ratio of (a) Consolidated EBITDA for the period of
                  four consecutive fiscal quarters of the Borrower ending on, or
                  most recently preceding, such day, PLUS Consolidated Rent
                  Expense for such period MINUS Consolidated Capital
                  Expenditures for such period, to (b) the sum of (i)
                  Consolidated Interest Expense for such period, PLUS (ii)
                  Consolidated Rent Expense for such period, PLUS (iii)
                  Consolidated Scheduled Funded Debt Payments for such period,
                  PLUS (iv) Consolidated Cash Dividends for such period."

                  (d)      The definition of "Life Insurance Assignment"
         contained in Section 1.1 of the Credit Agreement is hereby deleted
         therefrom in its entirety.

                  (e)      The definition of "Life Insurance Policy" contained
         in Section 1.1 of the Credit Agreement is hereby deleted in its
         entirety.

                  (f)      The definition of "Permitted Acquisition" contained
         in Section 1.1 of the Credit Agreement is hereby deleted therefrom in
         its entirety and the following definition is hereby substituted in lieu
         thereof:

                  ""PERMITTED ACQUISITION" shall mean an acquisition by the
                  Borrower or any Wholly Owned Domestic Subsidiary of the
                  Borrower of the Capital Stock or all or substantially all of
                  the Property of another Person (including by merger or
                  consolidation or by incorporation of a new Subsidiary) for up
                  to the fair market value of the Capital Stock or Property
                  acquired, PROVIDED, THAT, (a) the Capital Stock or Property
                  acquired in such acquisition relates directly to or is
                  strategically related to the business of the Borrower or any
                  of its Subsidiaries as existing on the Effective Date, (b) any
                  Indebtedness issued, incurred (other than under this
                  Agreement) or




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                  assumed by the Borrower and its Subsidiaries on a consolidated
                  basis from such acquisition (as permitted hereunder) shall not
                  in the aggregate exceed $5,000,000, (c) the Agent shall have
                  received all items in respect of the Capital Stock or Property
                  acquired in such acquisition (and/or the seller thereof)
                  required to be delivered by the terms of Section 6.11, (d) in
                  the case of an acquisition of the Capital Stock of another
                  Person, (i) the board of directors (or other comparable
                  governing body) of such other Person shall have duly approved
                  such acquisition and (ii) the Capital Stock acquired shall
                  constitute 100% of the Total Voting Power and ownership
                  interest of the issuer thereof, (e) no Default or Event of
                  Default shall have occurred and be continuing immediately
                  before or immediately after giving effect to such acquisition
                  and the Borrower shall have delivered to the Agent a Pro Forma
                  Compliance Certificate demonstrating that, upon giving effect
                  to such acquisition on a Pro Forma Basis, the Borrower shall
                  be in compliance with all of the financial covenants set forth
                  in Section 7.18 as of the last day of the most recent period
                  of four consecutive fiscal quarters of the Borrower which
                  precedes or ends on the date of such acquisition and with
                  respect to which the Agent has received the Required Financial
                  Information, (f) the representations and warranties made by
                  the Credit Parties in each Credit Document shall be true and
                  correct in all material respects as of the date of such
                  acquisition (as if made on such date after giving effect
                  thereto) except to the extent such representations and
                  warranties expressly relate to an earlier date (in which case
                  such representations and warranties shall be true and correct
                  in all material respects at and as of such earlier date), (g)
                  after giving effect to such acquisition, the Revolving
                  Committed Amount shall be at least $5,000,000 greater than the
                  sum of all Revolving Loans outstanding PLUS all LOC
                  Obligations outstanding, PLUS all Competitive Bid Loans
                  outstanding, (h) the aggregate consideration (including cash,
                  assumption of indebtedness and non-cash consideration) for any
                  single acquisition (or series of related acquisitions) shall
                  not exceed $30,000,000 and (i) the aggregate cash
                  consideration for any single acquisition (or series of related
                  acquisitions) shall not exceed $10,000,000 and the aggregate
                  cash consideration for all such acquisitions occurring during
                  any calendar year of the Borrower during the term hereof shall
                  not exceed $30,000,000."



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                  (g)      The definition of "Permitted Investments" contained
         in Section 1.1 of the Credit Agreement is hereby deleted therefrom in
         its entirety and the following definition is hereby substituted in lieu
         thereof:

                  ""PERMITTED INVESTMENTS" shall mean Investments which consist
                  of (a) cash or Cash Equivalents; (b) trade accounts receivable
                  (and related notes and instruments) arising in the ordinary
                  course of business in accordance with customary trade terms;
                  (c) Investments existing as of the Effective Date and set
                  forth in SCHEDULE 1.1A; (d) Guaranty Obligations permitted by
                  Section 7.1; (e) advances or loans to directors, officers,
                  employees, agents, customers or suppliers that do not exceed
                  $250,000 in the aggregate at any one time outstanding for all
                  of the Borrower and its Subsidiaries; (f) Investments by the
                  Borrower or any Wholly Owned Subsidiary in Subsidiaries of the
                  Borrower or by any Subsidiary in the Borrower evidenced by
                  Intercompany Notes pledged to the Agent for the benefit of the
                  Secured Parties; PROVIDED, THAT, (i) the aggregate principal
                  amount of such Intercompany Notes issued by Foreign
                  Subsidiaries of the Borrower to the Borrower or to any
                  Domestic Subsidiary of the Borrower and outstanding at any
                  time shall not exceed $5,000,000 in the aggregate, (ii) no
                  Investments shall be made in the Capital Stock of any Foreign
                  Subsidiary except as a Permitted Acquisition; and (iii)
                  Investments in a Wholly Owned Subsidiary are permitted only so
                  long as such person remains a Wholly Owned Subsidiary; (g)
                  Investments by the Borrower or any Wholly Owned Subsidiary in
                  any Person; PROVIDED, THAT, the aggregate consideration for
                  all such Investments shall not exceed $8,000,000; or (h)
                  Permitted Acquisitions."

                  (h)      Section 5.25(a) of the Credit Agreement is hereby
         deleted therefrom in its entirety and the following definition is
         hereby substituted in lieu thereof:

                           "5.25 SECURITY DOCUMENTS. (a) The Pledge Agreement is
                  effective to create in favor of the Agent, for the ratable
                  benefit of the Secured Parties, a legal, valid and enforceable
                  first priority security interest in 100% of the issued and
                  outstanding Capital Stock of all Subsidiaries (PROVIDED that
                  no shares of Capital Stock of any issuer incorporated in a
                  jurisdiction outside of the United States of America shall be
                  pledged to the extent that the aggregate amount of shares of
                  Capital Stock of such issuer pledged under the Pledge
                  Agreement would exceed 65% of the Capital Stock of such issuer
                  to the extent, and for so long as, the pledge of any greater
                  percentage would have adverse tax consequences for the
                  pledging party), and, when the Pledged Securities (as defined
                  in the Pledge Agreement) are delivered to the Agent, the
                  Pledge Agreement shall constitute a fully perfected Lien on,
                  and security interest in, all right, title and interest of the
                  grantors thereunder in such of the Collateral in which a
                  security interest can be perfected under Article 8 or 9 of the
                  Uniform Commercial Code prior and superior in right to any
                  other Person, other than with respect to Permitted Liens."

                  (i)      Section 6.12 of the Credit Agreement is hereby
         deleted therefrom in its entirety.




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                  (j)      Section 7.7 of the Credit Agreement is hereby deleted
         therefrom in its entirety and the following definition is hereby
         substituted in lieu thereof:

                           "7.7 RESTRICTED PAYMENTS. None of the Credit Parties
                  will, directly or indirectly, declare, order, make or set
                  apart any sum for or pay any Restricted Payment, except (a)
                  dividends payable solely in common stock of such Person, (b)
                  dividends or other distributions payable to (i) the Borrower
                  or any Wholly Owned Domestic Subsidiary of the Borrower and
                  (ii) the shareholders of the common stock of the Borrower, (c)
                  repurchases of common stock of the Borrower from any employee
                  of the Credit Parties upon the termination of employment of
                  such employee; PROVIDED, THAT, the aggregate amount paid in
                  all such repurchases shall not exceed $750,000 in any fiscal
                  year of the Borrower during the term of this Amended
                  Agreement, (d) repurchases of common stock of the Borrower in
                  addition to such repurchases permitted pursuant to clause (c)
                  of this Section 7.7; PROVIDED, THAT the aggregate amount paid
                  in all such repurchases permitted pursuant to this clause (d)
                  shall not exceed $5,000,000; PROVIDED, THAT, in each case as
                  set forth in clauses (a) through (d) above, no Default or
                  Event of Default has occurred and is continuing at such time
                  or would exist after giving effect to such payment on a pro
                  forma basis as if it had been made on the first day of the
                  most recently completed period of four consecutive fiscal
                  quarters of the Borrower."

         SECTION 2. REPRESENTATIONS AND WARRANTIES. The Borrower hereby
represents and warrants to the Agent and the Lenders, as follows:

                  (a)      The Borrower is in compliance with all the terms and
         conditions of the Credit Agreement on its part to be observed or
         performed. There exists no Default or Event of Default.

                  (b)      The execution, delivery and performance by the
         Borrower of this First Amendment have been duly authorized by the
         Borrower.

                  (c)      This First Amendment constitutes the legal, valid and
         binding obligation of the Borrower, enforceable against it in
         accordance with its terms.

                  (d)      The execution, delivery and performance by the
         Borrower of this First Amendment (i) do not conflict with or violate
         (A) any provision of law, statute, rule or regulation, or of the
         constitutive documents of the Borrower, (B) any order of any
         Governmental Authority or (C) any provision of any indenture, agreement
         or other instrument to which the Borrower is a party or by which it or
         any of its property may be bound and (ii) do not require any consents
         under, result in a breach of or constitute (with notice or lapse of
         time or both) a default under any such indenture, agreement or
         instrument.

         SECTION 3. EFFECTIVENESS. This First Amendment shall become effective
only upon satisfaction of the following conditions precedent (the first date
upon which each such condition has been satisfied being herein called the
"AMENDMENT EFFECTIVE DATE").


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                  (a)      The Agent shall have received duly executed
         counterparts of this First Amendment which, when taken together, bear
         the authorized signatures of the Borrower and the Required Lenders.

                  (b)      The Agent shall be satisfied that the representations
         and warranties set forth in Section 2 are true and correct on and as of
         the Amendment Effective Date.

                  (c)      There shall not be any action pending or any
         judgment, order or decree in effect which, in the judgment of the Agent
         or the Lenders, is likely to restrain, prevent or impose materially
         adverse conditions upon performance by the Borrower of its obligations
         under the Amended Credit Agreement.

                  (d)      The Agent shall have received such other documents,
         legal opinions, instruments and certificates relating to this First
         Amendment as they shall reasonably request and such other documents,
         legal opinions, instruments and certificates shall be satisfactory in
         form and substance to the Agent and the Lenders. All corporate and
         other proceedings taken or to be taken in connection with this First
         Amendment and all documents incidental thereto, whether or not referred
         to herein, shall be satisfactory in form and substance to the Agent and
         the Lenders.

         SECTION 4. APPLICABLE LAW. THIS FIRST AMENDMENT SHALL BE GOVERNED BY,
AND CONSTRUED IN ACCORDANCE WITH, THE LAWS OF THE STATE OF NORTH CAROLINA.

         SECTION 5. EXPENSES. The Borrower shall pay all fees and expenses of
counsel to the Agent outstanding as of the date hereof and all reasonable
out-of-pocket expenses incurred by the Agent and the Lenders in connection with
the preparation, negotiation, execution, delivery and enforcement of this First
Amendment. The agreement set forth in this Section 5 shall survive the
termination of this First Amendment and the Amended Credit Agreement.

         SECTION 6. COUNTERPARTS. This First Amendment may be executed in any
number of counterparts, each of which shall constitute an original but all of
which when taken together shall constitute but one agreement. Delivery of an
executed counterpart of a signature page to this First Amendment by telecopier
shall be effective as delivery of a manually executed counterpart of this First
Amendment.



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         SECTION 7. CREDIT AGREEMENT. Except as expressly set forth herein, the
amendments provided herein shall not by implication or otherwise limit,
constitute a waiver of, or otherwise affect the rights and remedies of the Agent
or the Lenders under the Credit Agreement, nor shall they alter, modify, amend
or in any way affect any of the terms, conditions, obligations, covenants or
agreements contained in the Credit Agreement. The amendments provided herein
shall apply and be effective only with respect to the provisions of the Credit
Agreement specifically referred to by such amendments. Except as expressly
amended herein, the Credit Agreement shall continue in full force and effect in
accordance with the provisions thereof. As used in the Credit Agreement, the
terms "Amended Agreement", "herein", "hereinafter", "hereunder", "hereto" and
words of similar import shall mean, from and after the date hereof, the Amended
Credit Agreement.



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         IN WITNESS WHEREOF, each of the parties hereto has caused a counterpart
of this First Amendment to be duly executed and delivered as of the date first
above written.



BORROWER:                          KENDLE INTERNATIONAL INC.
                                   an Ohio corporation


                                   By: /s/ Timothy M. Mooney
                                       ---------------------------------------- 
                                       Name: Timothy M. Mooney
                                       Title: Vice President and CFO



LENDERS:                           NATIONSBANK, N.A.,
                                   individually in its capacity as a
                                   Lender and in its capacity as Agent and
                                   Issuing Lender


                                   By: /s/ Michael S. Sylvester
                                       ---------------------------------------- 
                                       Name: Michael S. Sylvester
                                       Title: 


                                   BANK ONE, N.A., as a Lender


                                   By: /s/ Richard Kuertz
                                       ---------------------------------------- 
                                       Name: Richard Kuertz
                                       Title: 


                                   FIFTH THIRD BANK, as a Lender


                                   By: /s/ H. Lytle Thomas
                                       ---------------------------------------- 
                                       Name: H. Lytle Thomas
                                       Title: