Exhibit 10.1

SIXTH AMENDMENT

TO

LOAN AND SECURITY AGREEMENT

THIS SIXTH AMENDMENT to Loan and Security Agreement (this “Amendment”) is
entered into this 2nd day of January, 2007, by and between Silicon Valley Bank
(“Bank”) and Pharsight Corporation, a Delaware corporation (“Borrower”) whose
address is 321 East Evelyn Avenue, 3 rd Floor, Mountain View, California 94041.

RECITALS

A. Bank and Borrower have entered into that certain Amended and Restated Loan
and Security Agreement dated as of May 27, 2004, as amended by that certain Loan
Modification Agreement by and between Bank and Borrower dated as of February 10,
2005, as amended by that certain Loan Modification by and between Bank and
Borrower dated as of May 26, 2005, as amended by that certain Loan Modification
Agreement by and between Bank and Borrower dated as of June 20, 2005, by that
certain Fourth Amendment to Loan and Security Agreement by and between Bank and
Borrower dated as of July 14, 2005 and as further amended by that certain Fifth
Amendment to Loan and Security Agreement by and between Bank and Borrower dated
as of June 12, 2006 (as the same may from time to time be further amended,
modified, supplemented or restated, the “Loan Agreement”).

B. Bank has extended credit to Borrower for the purposes permitted in the Loan
Agreement.

C. Borrower has requested that Bank amend the Loan Agreement to (i) lower the
interest rate payable on the Advances, Term Loan 2 and Equipment Advances,
(ii) extend the Revolving Maturity Date and (iii) make certain other revisions
to the Loan Agreement as more fully set forth herein.

D. Bank has agreed to so amend certain provisions of the Loan Agreement, but
only to the extent, in accordance with the terms, subject to the conditions and
in reliance upon the representations and warranties set forth below.

AGREEMENT

NOW, THEREFORE, in consideration of the foregoing recitals and other good and
valuable consideration, the receipt and adequacy of which is hereby
acknowledged, and intending to be legally bound, the parties hereto agree as
follows:

1. Definitions. Capitalized terms used but not defined in this Amendment shall
have the meanings given to them in the Loan Agreement.

2. Amendments to Loan Agreement.

2.1 Section 2.4 (Interest Rate, Payments). Section 2.4(a) is amended in part to
read as follows:

(a) Interest Rate. Effective as of December 15, 2006, (i) Advances, Term Loan 2
and Equipment Advances accrue interest on the outstanding principal balance at a
per annum rate of 0.375% above the Prime Rate.

2.2 Section 2.4 (Interest Rate, Payments). The first sentence under
Section 2.4(b) is hereby amended in its entirety and replaced with the
following:

(b) Payments. Interest due on the Committed Revolving Line is payable on the
24th of each month.

2.3 Section 2.5 (Fees). Notwithstanding anything under Section 2.5(a), Borrower
will pay to Bank an anniversary fee of $7,500 on May 24, 2007. Bank is hereby
authorized to debit Borrower’s account number                          for the
anniversary fee on May 24, 2007.

2.4 Section 6.2 (Financial Statements, Reports, Certificates). Section 6.2(e) is
hereby amended in its entirety and replaced with the following:

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(e) Allow Bank to audit Borrower’s Collateral at Borrower’s expense. Such audits
will be conducted not more often than once a year unless an Event of Default has
occurred and is continuing.

2.5 Section 6.6 (Primary Accounts). Section 6.6 is amended in its entirety and
replaced with the following:

Borrower will maintain all of its primary operating and securities accounts at
Bank or its affiliates.

2.6 Section 6.7 (Financial Covenants). Section 6.7(ii) entitled “Tangible Net
Worth” is hereby deleted in its entirety.

2.7 Section 13 (Definitions). Sub-letter (e) of the defined term “Eligible
Accounts” is hereby amended to include the following:

Notwithstanding the forgoing, if Borrower’s Adjust Quick Ratio is equal to 2.50
to 1.00 or greater, Bank may include those accounts from account debtors does
not have it principal place of business in the United States, provided, however,
if the Adjusted Quick Ratio is less than 2:50 to 1:00, then those accounts will
be at Bank sole discretion.

2.8 Section 13. (Definitions). The following term and its respective definition
set forth in Section 13.1 is amended in its entirety and replaced with the
following:

“Revolving Maturity Date” is May 24, 2008.

3. Limitation of Amendments.

3.1 The amendments set forth in Section 2, above, are effective for the purposes
set forth herein and shall be limited precisely as written and shall not be
deemed to (a) be a consent to any amendment, waiver or modification of any other
term or condition of any Loan Document, or (b) otherwise prejudice any right or
remedy which Bank may now have or may have in the future under or in connection
with any Loan Document.

3.2 This Amendment shall be construed in connection with and as part of the Loan
Documents and all terms, conditions, representations, warranties, covenants and
agreements set forth in the Loan Documents, except as herein amended, are hereby
ratified and confirmed and shall remain in full force and effect.

4. Representations and Warranties. To induce Bank to enter into this Amendment,
Borrower hereby represents and warrants to Bank as follows:

4.1 Immediately after giving effect to this Amendment (a) the representations
and warranties contained in the Loan Documents are true, accurate and complete
in all material respects as of the date hereof (except to the extent such
representations and warranties relate to an earlier date, in which case they are
true and correct as of such date), and (b) no Event of Default has occurred and
is continuing;

4.2 Borrower has the power and authority to execute and deliver this Amendment
and to perform its obligations under the Loan Agreement, as amended by this
Amendment;

4.3 The organizational documents of Borrower delivered to Bank on May 27, 2004
remain true, accurate and complete and have not been amended, supplemented or
restated and are and continue to be in full force and effect;

4.4 The execution and delivery by Borrower of this Amendment and the performance
by Borrower of its obligations under the Loan Agreement, as amended by this
Amendment, have been duly authorized;

4.5 The execution and delivery by Borrower of this Amendment and the performance
by Borrower of its obligations under the Loan Agreement, as amended by this
Amendment, do not and will not contravene (a) any law or regulation binding on
or affecting Borrower, (b) any contractual restriction with a Person binding on
Borrower, (c) any order, judgment or decree of any court or other governmental
or public body or authority, or subdivision thereof, binding on Borrower, or
(d) the organizational documents of Borrower;

4.6 The execution and delivery by Borrower of this Amendment and the performance
by Borrower of its obligations under the Loan Agreement, as amended by this
Amendment, do not require any order, consent, approval, license, authorization
or validation of, or filing, recording or registration with, or exemption by any
governmental or public body or authority, or subdivision thereof, binding on
either Borrower, except as already has been obtained or made; and

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4.7 This Amendment has been duly executed and delivered by Borrower and is the
binding obligation of Borrower, enforceable against Borrower in accordance with
its terms, except as such enforceability may be limited by bankruptcy,
insolvency, reorganization, liquidation, moratorium or other similar laws of
general application and equitable principles relating to or affecting creditors’
rights.

5. Integration. This Amendment and the Loan Documents represent the entire
agreement about this subject matter and supersede prior negotiations or
agreements. All prior agreements, understandings, representations, warranties,
and negotiations between the parties about the subject matter of this Amendment
and the Loan Documents merge into this Amendment and the Loan Documents.

6. Counterparts. This Amendment may be executed in any number of counterparts
and all of such counterparts taken together shall be deemed to constitute one
and the same instrument.

7. Effectiveness. This Amendment shall be deemed effective upon the due
execution and delivery to Bank of this Amendment by each party hereto.

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be duly
executed and delivered as of the date first written above.

 

BANK     BORROWER Silicon Valley Bank     Pharsight Corporation By:  

/s/ Liam Fairbairn

    By:  

/s/ William Frederick

Name:   Liam Fairbairn     Name:   William Frederick Title:   Relationship
Manager     Title:   Chief Financial Officer