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                                                                EXHIBIT 10.46
                                       
                          FIRST AMENDMENT TO SUBLEASE



     THIS FIRST AMENDMENT TO SUBLEASE ("Amendment") effective as of February 
27, 1998 ("Effective Date"), is entered into by and between Molecular 
Biosystems, Inc., a Delaware corporation (the "Sublessor"), and Dura 
Pharmaceuticals, Inc., a Delaware corporation (the "Sublessee"). Sublessor 
and Sublessee are collectively hereinafter referred to as the "parties."

                                    RECITALS

          B.  Sublessor and Sublessee entered into a written Sublease 
effective October 1, 1997 (the "Sublease") pursuant to which Sublessor 
subleased to Sublessee and Sublessee subleased from Sublessor the Premises 
described therein. Sublessor holds the Premises and certain other premises 
(collectively, the "Master Premises") pursuant to a certain Master Lease made 
as of June 19, 1995 ("Master Lease"), by and between Radnor/Collins/Sorrento 
Partnership, as "Lessor," and Sublessor under this Sublease, as "Lessee." 

          C.  Sublessor and Sublessee now wish to make modifications to the 
Sublease to expand the Premises, revise the rental rate for the Premises, and 
to extend the Term of the Sublease, all in accordance with the terms and 
conditions set forth herein.

          D.  The parties now wish to amend the Sublease to reflect these 
changes and to make other modifications in consideration therefor.

     NOW, THEREFORE, in consideration of the above Recitals, and the mutual 
covenants contained herein, the parties agree as follows:

          1.  LEASE AMENDMENT.  A copy of the Sublease is attached hereto and 
incorporated herein as EXHIBIT A.  Except as expressly provided in this 
Amendment, the Sublease shall remain unmodified, in full force and effect.  
The capitalized terms used herein shall have the meanings ascribed to them in 
the Sublease unless otherwise indicated.  To the extent that there is any 
conflict between this Amendment and the Sublease, the provisions of this 
Amendment shall prevail.


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          2.  PREMISES.  

               2.1  Effective April 15, 1998 or such earlier date as 
Sublessor elects by five (5) days prior written notice to Sublessee ("First 
Expansion Date"), the Premises shall be expanded to include the entire Master 
premises except the Second Expansion Space (the "First Expansion Space") of 
the Building, as more particularly shown in EXHIBIT B.

               2.2  Effective June 1, 1998 or such earlier date as Sublessor 
elects by ten (10) days prior written notice to Sublessee ("Second Expansion 
Date"), the Premises shall be further expanded to include the entire Master 
Premises of Sublessor under the Master Lease as set forth in Section 2.1 of 
the Master Lease.  The space added to the Premises pursuant to this Section 
2.2 shall be known as the "Second Expansion Space."  Collectively, both the 
First Expansion Space and the Second Expansion Space shall be known as the 
"Expansion Space."
  
          3.  PROPORTIONATE SHARE.  

               3.1  On the First Expansion Date, the Sublessee's 
Proportionate Share, as set forth in the Basic Sublease Information and 
Section 1.1 of the Sublease shall be increased to ninety-five percent (95%).  

               3.2  On and after the Second Expansion Date, the Sublessee's 
Proportionate Share shall be increased to one hundred percent (100%).

          4.  BASE RENT.  

               4.1  From and after the First Expansion Date, the Base Rent 
for the Premises shall be $1.07 per rentable square foot, or a total of 
Fifty-Five Thousand Nine Hundred Seventy-Three Dollars and Eighty-Four Cents 
($55,973.84) per month.

               4.2  From and after the Second Expansion Date, the Base Rent 
for the Premises shall be Fifty-Eight Thousand Five Hundred Forty-One Dollars 
and Eighty-Four Cents ($58,541.84) per month.

               4.3  On July 1, 1998, and each anniversary thereof, 
Sublessee's Base Rent shall increase by four percent (4%) of Sublessee's Base 
Rent for the preceding month.

          5.  TERM.  The Term of the Sublease shall expire on December 
31,1999.

          6.  LIMITATION OF EXCLUSIONS.  From and after the Second Expansion 
Date, Sections 17.1 and 17.4 shall be incorporated into the Sublease, 
notwithstanding Section 7.2 of the Sublease.  

          7.  SUBLESSOR'S OBLIGATIONS.  Section 7.4 of the Sublease shall be 
deleted in its entirety and the following shall be substituted therefor:


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          7.4  SUBLESSOR'S OBLIGATIONS.  Sublessee acknowledges that
               Sublessor shall be under no obligation to provide any
               services or satisfy any obligations or covenants of
               Master Landlord contained in the Master Lease;
               provided, however, Sublessor, upon written notice by
               Sublessee shall promptly and diligently attempt to
               enforce all obligations of Master Landlord under the
               Master Lease, provided that Sublessee reimburses
               Sublessor for all reasonable costs and expenses
               incurred in connection therewith.  

          8.  PHYSICAL CONDITION.  Sublessee and Sublessor recognize and 
agree that Sublessor would not sublease the Expansion Space to Sublessee and 
Sublessee would not sublease the Expansion Space from Sublessor except on an 
"as is" basis and acknowledges that neither Sublessee nor Sublessor has made 
any representations of any kind, express or implied, in connection with the 
Improvements or physical conditions on, or bearing on, the Expansion Space, 
including without limitation the suitability of the Expansion Space for 
Sublessee's purposes.  Sublessee further recognizes and agrees that neither 
Sublessor nor Master Landlord shall be required to perform any work of 
construction, alteration or maintenance of or to the Expansion Space except 
as set forth in the Master Lease.

          9.  SUBLESSEE'S ADDITIONAL OBLIGATIONS.  From and after the Second 
Expansion Date, Sublessee shall expressly assume and shall be directly 
responsible for all Lessee's obligations under Section 11 of the Master 
Lease. As Sublessor in its sole discretion may from time to time demand, 
Sublessee shall provide Sublessor within five (5) business days with copies 
of all contracts, invoices, accounting records and any other records 
associated with Sublessee's fulfillment of the Lessee's obligations under 
Section 11 of the Master Lease.  However, at Sublessor's sole discretion, 
Sublessor may choose to directly fulfill any or all of Sublessor's 
obligations under Section 11 of the Master Lease and be compensated for any 
such expenses reasonably incurred pursuant to Section 3.2 of the Sublease and 
Section 3.2 of this Amendment.  Any maintenance contracts entered into by 
Sublessee for obligations covered by this Section 9 shall by their terms be 
freely assignable to Sublessor, and Sublessee shall promptly assign any such 
contracts to Sublessor if Sublessor at its sole discretion so requests.

          10.  FORMER BUILDING AREA COMMON AREAS.   As of the Effective Date, 
Sublessor shall have no responsibility for the care, management or expenses 
of any portion of the Building Common Area incorporated into Sublessee's 
Premises pursuant to Sections 2.1 and 2.2 of this Amendment.  As of the 
Second Expansion Date, all Building Common Areas shall be included in the 
Premises, Sublessor shall have no maintenance, repair or other obligations in 
connection therewith and Sublessee shall have direct responsibility for 
repair and maintenance thereof, in accordance with the terms and conditions 
of the Sublease and the Master Lease.


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          11.  SECURITY DEPOSIT.   Upon executing this Amendment, Sublessee 
shall deposit with Sublessor a Security Deposit in the amount of Fifty-Eight 
Thousand Five Hundred Forty-One Dollars and Eighty-Four Cents ($58,541.84).  
The Security Deposit shall secure Sublessee's obligations under the Sublease 
to pay rent and other monetary amounts, to maintain the Premises and repair 
damages thereto, to surrender the Premises to Sublessor in clean and sanitary 
condition and to discharge Sublessee's other obligations hereunder.  
Sublessor may use and commingle the Security Deposit with other funds of 
Sublessor.  If Sublessee fails to perform Sublessee's obligations hereunder, 
Sublessor may, but without any obligation to do so, apply all or any portion 
of the Security Deposit towards fulfillment of Sublessee's unperformed 
obligations.  If Sublessor does so apply any portion of the Security Deposit, 
Sublessee shall immediately pay Sublessor a sufficient amount in cash to 
restore the Security Deposit to the full original amount.  In the event that 
Sublessor shall expend the same in order to cure Sublessee's default 
hereunder, Sublessee's failure to forthwith remit to Sublessor a sufficient 
amount in cash to restore the Security Deposit to the original sum deposited 
within five (5) days after Sublessee's receipt of notice from Sublessor that 
such amounts have been so expended shall constitute a material default of the 
Sublease.  The Security Deposit shall be held by Sublessor without liability 
for interest on the same.  Upon termination of this Lease, if Sublessee has 
then performed all of Sublessee's obligations hereunder, Sublessor shall 
return the Security Deposit to Sublessee.  If Sublessor sells or otherwise 
transfers Sublessor's rights or interest under this Lease, Sublessor may 
deliver the Security Deposit to the transferee, whereupon Sublessor shall be 
released from any further liability to Sublessee with respect to the Security 
Deposit.

          12.  NOTICES.  Sublessee shall concurrently send copies to 
Sublessor, at Sublessor's Address for Notice set forth in the Basic Sublease 
Information of the Sublease, of all notices Sublessee sends to Master 
Landlord and shall promptly send to Sublessor copies of all notices received 
from Master Landlord.

          13.  INDEMNIFICATION.  Sublessee shall indemnify, protect, defend 
and hold Sublessor harmless from and against any and all claims, liabilities, 
penalties, losses or expenses (including reasonable attorneys' fees and 
costs) arising in connection with Sublessee's breach or failure to perform 
any of Sublessee's obligations under the Sublease as modified by this 
Amendment and/or the Master Lease.  Sublessor shall indemnify, protect, 
defend and hold Sublessee harmless from and against any and all claims, 
liabilities, penalties, losses or expenses (including reasonable attorneys' 
fees and costs) arising in connection with Sublessor's breach or failure to 
perform any of Sublessor's obligations under the Sublease as modified by this 
Amendment and/or the Master Lease.
          

          14.  MASTER LANDLORD'S CONSENT.  This Amendment is conditioned upon 
receipt of Master Landlord's written approval of this Amendment prior to the 
First Expansion Date.  If Master Landlord withholds its consent, this 
Amendment shall be deemed void and of no effect.


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          15.  AUTHORITY; COUNTERPARTS.  Each person executing this Amendment 
on behalf of a party represents that he or she is authorized and empowered to 
do so and to thereby bind the party on whose behalf he or she is signing.  
This Amendment may be executed in any number of counterparts, each of which 
shall be deemed to be an original and all of which together shall comprise 
but a single instrument.


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                      [SIGNATURE PAGE TO SUBLEASE AMENDMENT]

     IN WITNESS WHEREOF, the parties hereto have executed this Amendment 
effective as of the date and year hereinabove written.

                                             SUBLESSOR:

                                             MOLECULAR BIOSYSTEMS, INC.
                                             a Delaware corporation 


                                             By:  /s/ Gerard A. Wills
                                                  ---------------------------
                                                  Its Chief Financial Officer


                                             By:  ___________________________
                                                  Its___________
                                   


                                             SUBLESSEE:

                                             DURA PHARMACEUTICALS, INC.
                                             a Delaware corporation

                                             By:   /s/ M.R. Woodbury 
                                                   ---------------------------
                                                   Its Senior Vice President


                                             By:  ___________________________
                                                  Its___________



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