DURECT CORPORATION



                   AMENDMENT TO SECOND AMENDED AND RESTATED

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                          INVESTORS' RIGHTS AGREEMENT

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     This Amendment to Second Amended and Restated Investors' Rights Agreement

(the "Agreement") is made as of the 14th day of April, 2000, by and among Durect

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Corporation, a Delaware corporation (the "Company"), and the holders of a

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majority of the Registrable Securities outstanding as of the date hereof (as

such term is defined in the Rights Agreement).



                                   RECITALS

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     A.  The Company, Thomas A. Schreck, James E. Brown, Felix Theeuwes (the

"Founders"), the holders of the Company's Series A-1 Preferred Stock, the

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holders of the Company's Series A-2 Preferred Stock, the holders of the

Company's Series B Preferred Stock, the holders of the Company's Series B-1

Preferred Stock and the holders of the Company's Series C Preferred Stock

(together the "Preferred Holders") have previously entered into a Second Amended

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and Restated Investor's Rights Agreement dated as of March 28, 2000 (the "Rights

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Agreement"), pursuant to which the Company granted the Founders and the

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Preferred Holders certain rights.



     B.  The Company and ALZA Corporation ("ALZA") have entered into that

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certain Second Amended and Restated Development and Commercialization Agreement

(the "Development and Commercialization Agreement") effective April 28, 1999,

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pursuant to which the Company has issued to ALZA 1,000,000 shares of the

Company's Common Stock pursuant to a Common Stock Purchase Agreement dated April

14, 2000 (the "Common Stock Purchase Agreement"), and a warrant to purchase

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1,000,000 shares of the Company's Common Stock (the "Warrant").  Pursuant to the

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Development and Commercialization Agreement, the Company has agreed to amend the

Rights Agreement to provide ALZA certain rights to register shares of the

Company's Common Stock issued pursuant to the Common Stock Purchase Agreement or

issued or issuable upon exercise of the Warrant.



     C.  The Company, the Founders and the Preferred Holders each desire to

amend the Rights Agreement to add the shares of the Company's Common Stock

issuable upon exercise of the Warrant to the definition of Registrable

Securities under the Rights Agreement.



                                   AGREEMENT

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     The parties hereby agree as follows:



     1.  Amendment.

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         (a)   Section 1.1(b) of the Rights Agreement is hereby amended and

restated to read in its entirety as follows:

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         "(b)  The term "Registrable Securities" means (i) the shares of common

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stock, par value $0.0001 ("Common Stock") (A) issuable or issued upon conversion

of the Series A-1, Series A-2, Series B, Series B-1 and Series C Preferred

Stock, (B) issued to ALZA Corporation pursuant to that certain Common Stock

Purchase Agreement dated April 14, 2000 or (C) issuable or issued upon exercise

of that certain warrant issued to ALZA Corporation dated April 14, 2000, and any

successor Warrant issued upon transfer or exchange thereof, provided, however,

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that for the purposes of Sections 1.2, 1.4, 1.7(a), 1.7(c), 1.13 and 2 the

Series B-1 Preferred Stock shall not be deemed Registrable Securities and the

Series B-1 Holders shall not be deemed Holders (ii) the shares of Common Stock

issued to the Founders (the "Founders' Stock"), provided, however, that for the

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purposes of Sections 1.2, 1.4 and 1.13 the Founders' Stock shall not be deemed

Registrable Securities and the Founders shall not be deemed Holders, and (iii)

any other shares of Common Stock of the Company issued as (or issuable upon the

conversion or exercise of any warrant, right or other security which is issued

as) a dividend or other distribution with respect to, or in exchange for or in

replacement of, the shares listed in (i) and (ii); provided, however, that the

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