Exhibit
10.45  FIRST
AMENDMENT  THIS FIRST
AMENDMENT dated as of October 27, 2008 (this Amendment), amongAMYLIN PHARMACEUTICALS, INC.,
a Delaware corporation (the Company),
each of the Companys subsidiaries listed on the signature pages hereto
(collectively, together with the Company, the Borrowers
and each a Borrower), the Lenders (as
defined below) party hereto, and BANK
OF AMERICA, N.A., as Administrative Agent, Collateral Agent and L/C
Issuer (in such capacity, the Administrative Agent)
for the Lenders.  W I T N E S S E T H:  WHEREAS, the
Borrowers are a party to a Credit Agreement, dated as of December 21,
2007, among the Borrowers, the lenders from time to time party thereto (the Lenders), the Administrative Agent,
and the other agents, lead arranger and book manager party thereto (the Existing Credit Agreement).
Capitalized terms used and not otherwise defined herein shall have the meanings
assigned to such terms in the Existing Credit Agreement;  WHEREAS, the Borrowers
and the Administrative Agent are parties to a Pledge and Security Agreement,
dated as of December 21, 2007 (the Existing Security
Agreement);  and  WHEREAS, the parties hereto have agreed, subject to
the terms and conditions hereof, to amend and modify the Existing Credit
Agreement and the Existing Security Agreement as provided herein;  NOW THEREFORE,
for good and valuable consideration, the receipt and sufficiency of which are
hereby acknowledged, the parties hereto hereby agree as follows:  SECTION 1.01.Amendment
to Section 2.07 of the Existing Credit Agreement.  Section 2.07(a) of the Existing
Credit Agreement is hereby deleted in its entirety and replaced by the
following:  (a) Term
Loans.  The Borrowers shall repay to
the Term Lenders the aggregate principal amount of all Term Loans outstanding
on each quarterly date set forth below in the respective amounts equal to the
percentages of the Term Loans set forth below (which amounts shall be reduced
as a result of the application of prepayments in accordance with the order of
priority set forth in Section 2.05):  Date
  
  AmountMarch 23, 2009
  
  6.25
  %June 22, 2009
  
  6.25
  %September 21, 2009
  
  6.25
  %December 21, 2009
  
  6.25
  %March 22, 2010
  
  6.25
  %June 21, 2010
  
  6.25
  %September 21, 2010
  
  6.25
  %December 21, 2010
  
  56.25
  %


provided, however, that
notwithstanding anything herein to the contrary, the final principal repayment
installment of the Term Loans shall be repaid on the Maturity Date for the Term
Facility and in any event shall be in an amount equal to the aggregate
principal amount of all Term Loans outstanding on such date.  SECTION 1.02.Amendment
to Section 6.01(c) of the Existing Credit Agreement.  Section 6.01(c) of the Existing
Credit Agreement is hereby amended by deleting the phrase but in any event at
least 60 days after the end of each fiscal year of the Company and replacing
it with but in any event no later than 60 days after the end of each fiscal
year of the Company.  SECTION 1.03.Amendment
to Section 6.02 of the Existing Credit Agreement.   The penultimate paragraph of Section 6.02
of the Existing Credit Agreement is hereby amended by (i) replacing the
reference to Section 6.02(d) in the first sentence thereof with a
reference to Section 6.02(c) and (ii) replacing the reference to Section 6.02(b)
in the second sentence thereof with a reference to Section 6.02(a).  SECTION 1.04.Amendment
to Section 8.02 of the Existing Credit Agreement. Section 8.02 of
the Existing Credit Agreement is hereby deleted in its entirety and replaced by
the following:  8.02Remedies
upon Event of Default.  If any Event
of Default occurs and is continuing, the Administrative Agent shall, at the
request of, or may, with the consent of, the Required Lenders, take any or all
of the following actions:  (a)declare
the commitment of each Lender to make Loans, any obligation of Bank of America
to enter into Secured Hedge Agreements under the Permitted FX Facility and any
obligation of the L/C Issuer to make L/C Credit Extensions to be terminated,
whereupon such commitments and obligation shall be terminated;  (b)declare
the unpaid principal amount of all outstanding Loans, all interest accrued and
unpaid thereon, and all other amounts owing or payable hereunder or under any
other Loan Document to be immediately due and payable, without presentment,
demand, protest or other notice of any kind, all of which are hereby expressly
waived by the Borrowers;  (c)require
that the Borrowers Cash Collateralize the L/C Obligations (in an amount equal
to the then Outstanding Amount thereof); and  (d)exercise
on behalf of itself, the Lenders and the L/C Issuer all rights and remedies
available to it, the Lenders and the L/C Issuer under the Loan Documents;  2


provided, however,
that upon the occurrence of an actual or deemed entry of an order for relief
with respect to the Borrowers under the Bankruptcy Code of the United States,
the obligation of each Lender to make Loans, any obligation of Bank of America
to enter into Secured Hedge Agreements under the Permitted FX Facility and any
obligation of the L/C Issuer to make L/C Credit Extensions shall automatically
terminate, the unpaid principal amount of all outstanding Loans and all
interest and other amounts as aforesaid shall automatically become due and
payable, and the obligation of the Borrowers to Cash Collateralize the L/C
Obligations as aforesaid shall automatically become effective, in each case
without further act of the Administrative Agent or any Lender.  SECTION 1.05.Amendment
to Schedule 10.02 to the Existing Credit Agreement.  Schedule 10.02 to the Existing Credit
Agreement shall be amended by adding the following website of the Company to
such Schedule:  www.amylin.com.  SECTION 1.06.Amendment
to Section 3.01 of the Existing Security Agreement.   The first sentence of the last paragraph of Section 3.01
of the Existing Security Agreement is hereby amended by deleting the reference
to clauses (i) through (iv) above with a reference to clauses (i) through
(iii) above.  SECTION 1.07.Amendment
to Section 4.01(f) of the Existing Security Agreement.  The first sentence of Section 4.01(f) of
the Existing Security Agreement is hereby amended by deleting the clause at the
end of such sentence that begins provided, however and
replacing it with the following clause:  ; provided, however,
that any Grantor shall not be required to deliver an Account Control Agreement
in respect of any Deposit Account that consists solely of Excluded Collateral
or is exclusively used for payroll, payroll taxes and other employee wage and
benefit payments to or for the benefit of the Grantors employees.  SECTION 1.08.Representations
and Warranties.  Each Borrower hereby
represents and warrants to the Administrative Agent and the Lenders, as
follows:  (a)The
representations and warranties of such Borrower contained in Article V of
the Existing Credit Agreement, as amended hereby (the Amended
Credit Agreement), or any other Loan Document (except for any
Secured Hedge Agreements or Secured Cash Management Agreements) or which are
contained in any document furnished at any time under or in connection
therewith are true and correct in all material respects on and as of the date
hereof and on and as of the Amendment Effective Date with the same effect as if
made on and as of the date hereof or the Amendment Effective Date, as the case
may be, except to the extent such representations and warranties specifically
refer to an earlier date, in which case they are true and correct in all
material respects as of such earlier date, and except that the representations
and warranties contained in Sections 5.05(a) and (b) of the Existing
Credit Agreement shall be deemed  3


to refer to the most recent statements furnished
pursuant to Sections 6.01(a) and (b) thereof, respectively.  (b)After
giving effect to this Amendment, each Loan Party is in compliance with all the
terms and conditions of the Amended Credit Agreement and the other Loan
Documents on its part to be observed or performed and no Default or Event of
Default has occurred or is continuing under the Amended Credit Agreement.  (c)The
execution, delivery and performance by such Borrower of this Amendment have
been duly authorized by such Borrower.  (d)Each
of this Amendment and the Amended Credit Agreement constitutes the legal, valid
and binding obligation of such Borrower, enforceable against such Borrower in
accordance with its terms.  (e)The
execution, delivery, performance and compliance with the terms and provisions
by such Borrower of this Amendment and the consummation of the transactions
contemplated herein, do not and will not: (i) contravene the terms of any
of such Borrowers Organization Documents; (ii) conflict with or result in
any breach or contravention of, or (except for the Liens created under the Loan
Documents) the creation of any Lien under, (A) any material Contractual
Obligation to which such Borrower is a party affecting such Borrower or the
properties of such Borrower or its Subsidiaries or (B) any order,
injunction, writ or decree of any Governmental Authority or any arbitral award
to which such Borrower or its property is subject or (C) violate any Law.  SECTION 1.09.Effectiveness.  This 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):  (a)The
Administrative Agent shall have received duly executed counterparts of this
Amendment which, when taken together, bear the authorized signatures of the
Borrower, the Administrative Agent and the Required Lenders.  (b)The
Administrative Agent on behalf of the Lenders shall have received such other
documents, instruments and certificates as they shall reasonably request and
such other documents, instruments and certificates shall be satisfactory in
form and substance to the Lenders and their counsel.  All corporate and other proceedings taken or
to be taken in connection with this Amendment and all documents incidental
thereto, whether or not referred to herein, shall be satisfactory in form and
substance to the Lenders and their counsel.  SECTION 1.10.APPLICABLE
LAW.  THIS AMENDMENT SHALL BE
GOVERNED BY, AND CONSTRUED IN ACCORDANCE WITH, THE LAWS OF THE STATE OF NEW
YORK.  SECTION 1.11.Costs
and Expenses.  The Borrowers promptly
shall pay all costs and expenses of the Administrative Agent in connection with
the preparation, execution and  4


delivery of this
Amendment and the other instruments and documents to be delivered hereunder
(including, without limitation, the reasonable fees and expenses of counsel for
the Administrative Agent) in accordance with the terms of Section 10.04(a) of
the Amended Credit Agreement.  SECTION 1.12.Loan
Document; Counterparts.  This
Amendment is and from and after the Amendment Effective Date shall be deemed to
be a Loan Document under the Amended Credit Agreement. This 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 by facsimile by any of the parties hereto of an executed
counterpart of this Amendment shall be as effective as an original executed
counterpart hereof and shall be deemed a representation that an original
executed counterpart hereof will be delivered, but the failure to deliver a
manually executed counterpart shall not affect the validity, enforceability or
binding effect of this Amendment.  SECTION 1.13.Existing
Credit Agreement and Existing Security Agreement.  Except as expressly set forth herein, the
amendment provided herein shall not, by implication or otherwise, limit,
constitute a waiver of, or otherwise affect the rights and remedies of the
Lenders or the Administrative Agent under the Existing Credit Agreement, the
Existing Security Agreement or any other Loan Document, nor shall it constitute
a waiver of any Default or Event of Default, nor shall it alter, modify, amend
or in any way affect any of the terms, conditions, obligations, covenants or
agreements contained in the Existing Credit Agreement, the Existing Security
Agreement or any other Loan Document. 
The amendment provided herein shall apply and be effective only with
respect to the provisions of the Existing Credit Agreement and the Existing
Security Agreement specifically referred to by such amendment.  Except to the extent a provision in the
Existing Credit Agreement or the Existing Security Agreement is expressly
amended herein, the Existing Credit Agreement and the Existing Security
Agreement shall continue in full force and effect in accordance with the
provisions thereof.  [Signature
pages follow]  5


IN WITNESS WHEREOF,
the parties hereto have caused this Amendment to be duly executed by their duly
authorized officers, all as of the date first above written.   AMYLIN PHARMACEUTICALS, INC.,
  as a BorrowerBy:
  
  /s/ Mark FolettaName:
  Mark FolettaTitle:
  
  Senior Vice President,
  Finance and ChiefFinancial OfficerAMYLIN OHIO LLC, as a BorrowerBy:
  Amylin Pharmaceuticals, Inc.,its Sole ManagerBy:
  
  /s/ Mark FolettaName:
  Mark FolettaTitle:
  
  Senior Vice President,
  Finance and ChiefFinancial OfficerAMYLIN INVESTMENTS LLC, as a
  BorrowerBy:
  Amylin Pharmaceuticals, Inc.,its Sole ManagerBy:
  
  /s/ Mark FolettaName:
  Mark FolettaTitle:
  
  Senior Vice President,
  Finance and ChiefFinancial Officer  First Amendment to Credit
Agreement Signature Page


BANK OF AMERICA, N.A.,as
  Administrative AgentBy:
  
  /s/ Brenda H. LittleName:
  Brenda
  H. LittleTitle:
  
  Vice
  President  First Amendment to Credit
Agreement Signature Page


BANK OF AMERICA, N.A.,as a
  Revolving Credit Lender, L/C Issuer and Hedge Bank under the Permitted F/X
  FacilityBy:
  
  /s/ Karin S. BarnesName:
  Karin S. BarnesTitle:
  
  Senior Vice President  First Amendment to Credit
Agreement Signature Page


BANC OF AMERICA LEASING & CAPITAL, LLC,as a Term LenderBy:
  
  /s/ Lori J. NoberiniName:
  Lori J. NoberiniTitle:
  
  Vice President  First Amendment to Credit
Agreement Signature Page


SILICON VALLEY BANK, as a Term
  LenderBy:
  /s/ Sarah LarsonName:   Sarah LarsonTitle:     Relationship Manager  First Amendment to Credit
Agreement Signature Page


BMO CAPITAL MARKETS FINANCING, INC.,
  as a Term LenderBy:
  /s/ Andrew PlutaName:
  Andrew PlutaTitle:
  
  Vice
  President, Healthcare  First Amendment to Credit
Agreement Signature Page


FIRST BANK, as a Term LenderBy:
  
  /s/ Gilmore HectorName:
  Gilmore HectorTitle:
  
  Vice President  First Amendment to Credit
Agreement Signature Page


AIB DEBT MANAGEMENT, LIMITED,
  as a Term LenderBy:
  
  /s/ Mia BolinName:
  Mia BolinTitle:
  
  Assistant Vice President, Investment Advisor to AIB
  Debt Management, Limited   AIB DEBT MANAGEMENT, LIMITED,
  as a Term LenderBy:
  
  /s/ Eanna P. MulkereName:
  Eanna
  P. MulkereTitle:
  
  Assistant Vice President, Investment Advisor to AIB
  Debt Management, Limited  First Amendment to Credit
Agreement Signature Page