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                                                                   EXHIBIT 10.16

                           SECOND AMENDED AND RESTATED
                                 PROMISSORY NOTE

                                                                  April 1, 2003
$3,500,000.00                                              Southfield, Michigan

                  FOR VALUE RECEIVED, the undersigned ("OBLIGOR") promise(s) to
pay to the order of Fifth Third Bank (formerly Old Kent Bank) ("PAYEE"), the
principal amount of Three Million Five Hundred Thousand Dollars ($3,500,000.00)
and interest (computed on the basis of a 360-day year for the actual number of
days elapsed) on the unpaid outstanding balance at a variable rate per annum of
0.25% below the Index Rate (as defined below) from time to time in effect until
and after maturity. The interest rate on this Note shall be adjusted
contemporaneously with each change in Payee's announced "prime" rate to the
specified percentage below the Index Rate in effect on the date of adjustment.

                  Interest only shall be charged monthly to Obligor's checking
account no. 7511748571. If any installment of principal or interest is not paid
within (10) ten days after it is due, Obligor shall immediately pay to the
holder of this Note a late charge in an amount equal to the greater of $50.00 or
one-tenth (1/10th) of one percent (1%) of the unpaid principal balance as of the
date of the late charge is assessed. This is in addition to the holder's other
rights and remedies for default in payment of an installment of interest when
due.

                  INDEX RATE. As used in this Note, "INDEX RATE" means the rate
of interest announced from time to time by Payee, as its "prime" interest rate.

                  EXPENSES. Obligor shall reimburse Payee for all reasonable and
actual out-of-pocket expenses that have been or in the future are incurred by
Payee in connection with making the loan evidenced by this Note and any
renewals, extensions or modifications of it and in connection with taking any
security for it, including, without limitation, filing fees, attorney fees and
expenses and costs of credit reports, appraisals and the like.

                  LINE OF CREDIT. The principal of this Note may be borrowed,
repaid and reborrowed by Obligor from time to time, subject to the provisions of
the Agreement (as hereinafter defined). Payee's records shall be prima facie
evidence of all loans and repayments and of the indebtedness outstanding under
this Note at any time.

                  SECURITY. This Note and all obligations of Obligor under it
are secured by the Agreement (as hereinafter defined), any and all security
agreements, guaranties, mortgages, pledge agreements, assignments and all other
agreements and instruments that have been or in the future are given by Obligor
or any third party to Payee ("SECURITY DOCUMENTS"), including, but not limited
to, Security Documents given in connection with or referred to in any prior
promissory notes given to Payee by any Obligor and Security Documents that
secure any present or future guaranty of all or part of the indebtedness
evidenced by this Note. Payee shall have all of the rights and powers set forth
in the Security Documents and in any other written agreements that have been or
in the future are given to Payee by Obligor, as though they were fully set forth

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in this Note. As additional security for the payment of Obligor's obligations
under this Note, Obligor grants to Payee a security interest in all tangible and
intangible property of Obligor now or in the future in the possession of Payee.

                  DEFAULT AND ACCELERATION. Each of the following shall be an
event of default under this Note: (i) if default occurs in the payment of any
installment of principal or interest under this Note or of any late charge or
out-of-pocket expense at any time owing to Payee under this Note or in the
payment of any other indebtedness or obligation now or in the future owing by
Obligor to Payee, as and when it shall be or become due and payable whether by
acceleration or otherwise, and payee has failed to cure such default within five
(5) business days; (ii) if default occurs in the performance of any other
obligation to Payee under this Note or under any other documents executed
pursuant to the Loan Agreement, and default is not cured within the period
provided in the Agreement (as hereinafter defined).

                  AGREEMENT. This Note is given under a certain Loan Agreement
dated as of March 31, 2000 among Payee, Obligor and I-Flow Corporation, as
Guarantor, as it has been or in the future is amended, extended, or replaced
("AGREEMENT"), and the holder of this Note shall have all of the rights and
powers set forth in the Agreement as though they were set forth fully in this
Note. Reference is made to the Agreement for a statement of the terms and
conditions under which the principal of this Note and accrued interest on it may
become, or may be declared to be, immediately due and payable.

                  PLACE AND APPLICATION OF PAYMENTS. Each payment upon this Note
shall be made at Payee's address or any other place that the holder of this Note
directs in writing. Any payment upon this Note shall be applied first to any
expenses (including expenses of collection) then due and payable to Payee under
this Note, then to any unpaid late charges, then to any applicable prepayment
premium, then to any accrued and unpaid interest under this Note and then to the
unpaid principal balance. If Obligor at any time owes the holder of this Note
any indebtedness or obligation in addition to the indebtedness evidenced by this
Note, and if any indebtedness owed by Obligor to the holder is then in default,
then Obligor shall have no right to direct or designate the particular
indebtedness or obligation upon which any payment made by, or collected from,
Obligor or from any Guarantor or other security shall be applied. Obligor waives
any such right and agrees that the manner of application of any such payment, as
between or among such indebtedness and obligations, shall be determined solely
by the holder.

                  SETOFF. The holder of this Note shall have the right at any
time to set off any indebtedness that the holder then owes to Obligor against
any indebtedness evidenced by this Note that is then due and payable.

                  REMEDIES. The holder of this Note shall have all rights and
remedies provided by law and by agreement of Obligor. Any requirement of
reasonable notice with respect to any sale or other disposition of collateral
shall be met if the holder sends the notice at least ten (10) days before the
date of sale or other disposition. Obligor shall pay any and all reasonable and
actual expenses, including reasonable attorney fees and legal expenses, paid or
incurred by the holder in protecting and enforcing the rights of and obligations
to the holder under any provision of this Note or any Security Document.

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                  WAIVERS. No delay by the holder of this Note in the exercise
of any right or remedy shall operate as a waiver of it. No single or partial
exercise by the holder of any right or remedy shall preclude any other or future
exercise of it or the exercise of any other right or remedy. No waiver by the
holder of any default or of any provision of this Note shall be effective unless
in writing and signed by the holder. No waiver of any right or remedy on one
occasion shall be a waiver of that right or remedy on any future occasion.

                  Each person signing below as Obligor waives demand for
payment, presentment, notice of dishonor and protest of this Note and waives all
defenses based on suretyship or impairment of collateral. Each such person also
consents to any extension or postponement of time of its payment, to any
substitution, exchange or release of all or any part of any security given to
secure this Note, to the addition of any party to it and to the release,
discharge, waiver, modification or suspension of any rights or remedies against
any person who may be liable for the indebtedness evidenced by this Note.

                  GENERAL. Each of the persons signing below as Obligor is
primarily liable on this Note and (i) receipt of value by any one of them
constitutes receipt of value by both or all of them, (ii) their liability on
this Note is joint and several, and (iii) the term "OBLIGOR" means each of them
and all of them. In this Note, "MATURITY" means the time when the entire
remaining unpaid principal balance shall be or shall become due and payable for
any reason, including acceleration as provided above.

                  APPLICABLE LAW AND JURISDICTION. This Note shall be governed
by and interpreted according to the laws of the State of Michigan, without
giving effect to principles of conflict of laws. Obligor irrevocably agrees and
consents that any action against Obligor for collection or enforcement of this
Note may be brought in any state or federal court that has subject matter
jurisdiction and is located in, or whose district includes, Oakland County,
Michigan, and that any such court shall have personal jurisdiction over Obligor
for purposes of such action.

                  AMENDMENT AND RESTATEMENT. This Note is not a new Note, but
amends and restates that certain Amended and Restated Promissory Note (the
"Prior Note") given by the undersigned on April 1, 2002. This Note does not
constitute the extinguishment of the Prior Note, but represents a continuation
of the Prior Note. Any security interests granted or reaffirmed to Payee by any
of the other parties to secure the Prior Note or any other prior notes given by
the undersigned continue to secure this Note.

                                        INFUSYSTEM, INC.

                                        By: ____________________________________
                                            Steve Watkins
                                        Its: President

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                                                                     Exhibit 4.1

                                 AMENDMENT NO. 1

                                     TO THE

                                RIGHTS AGREEMENT

                          DATED AS OF DECEMBER 13, 2000

                                 BY AND BETWEEN

                         SPECTRUM PHARMACEUTICALS, INC.

                                       AND

                         U.S. STOCK TRANSFER CORPORATION

      On December 13, 2000, the Board of Directors of Spectrum Pharmaceuticals,
Inc., a Delaware corporation (the "Company") authorized and declared a dividend
distribution of one Right (as defined in the Rights Agreement) for each share of
its Common Stock, each Right initially representing the right to purchase
one-hundredth of a share of Series B Junior Participating Preferred Stock of the
Company, upon the terms set forth in a Rights Agreement dated as of December 13,
2000 by and between U.S. Stock Transfer Corporation (the "Rights Agent") and the
Company (the "Rights Agreement")

      The Company recently entered into a Preferred Stock and Warrant Purchase
Agreement dated April 29, 2003 (the "Purchase Agreement"), pursuant to which the
Company issued and sold shares of its Series D 8% Cumulative Convertible Voting
Preferred Stock (the "Series D Preferred Stock") and Series D Common Stock
Purchase Warrants (the "Warrants"). Pursuant to the terms of the Certificate of
Designation of the Series D Preferred Stock (the "Certificate of Designations"),
each holder of the Series D Preferred Stock has the right to receive, on the
Distribution Date (as defined in the Rights Agreement), without further action
by the Board, such number of Rights (as defined in the Rights Agreement) equal
to the number of Rights such holder would have held if, immediately prior to the
Distribution Date, all of the shares of Series D Preferred Stock had been
converted into shares of Common Stock at the then current Conversion Value (as
defined in the Certificate of Designations). Pursuant to the terms of the
Warrants, each holder of a Warrant has the right to receive, after the
Distribution Date, upon exercise of the Warrant, such number of Rights equal to
the number of Rights such holder would have held if, immediately prior to the
Distribution Date, the portion of this Warrant being exercised at such time had
been exercised and the Warrant Shares issuable upon such exercise were
outstanding immediately prior to the Distribution Date.

      Therefore, in order to give effect to the above terms of the Series D
Preferred Stock and the Warrants, the Company and U.S. Stock Transfer
Corporation hereby agreed to amend the Rights Agreement as follows:
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      1.    Amend Section 1(a) of the Rights Agreement to add the following
            separate paragraph at the end of the section:

            "Also, notwithstanding the foregoing, each of the Purchasers listed
on Schedule 1 to the Preferred Stock and Warrant Purchase Agreement dated April
29, 2003 (the "Purchase Agreement"), by and among the Company and the Purchasers
thereto, shall not be deemed to be an "Acquiring Person," by virtue of such
Purchaser acquiring Beneficial Ownership of shares of Common Stock pursuant to
the terms of the Purchase Agreement, the Certificate of Designations (the
"Certificate of Designations") of the Company's Series D 8% Cumulative
Convertible Voting Preferred Stock (the "Series D Preferred Stock"), the
Warrants (as defined in the Purchase Agreement) or the Placement Agent Warrants
issued or issuable to SCO Financial Group LLC, and/or its designees, pursuant to
that certain financial advisory agreement between the Company and SCO Financial
Group LLC, dated February 1, 2003 (the Warrants and the Placement Agent Warrants
hereinafter referred to as the "Warrant" if singular, or "Warrants" if plural).
However, this exception to the definition of "Acquiring Person" shall not affect
the determination of whether the Purchasers or any of them or SCO Financial
Group LLC, shall be an "Acquiring Person" as the result of any other acquisition
of Beneficial Ownership of shares of Common Stock."

      2.    Add subsection (d) to Section 3 of the Rights Agreement to read in
            its entirety as follows:

            "(d) Notwithstanding any of the foregoing, each record holder of
shares of Series D Preferred Stock has the right to receive, on the Distribution
Date, such number of Rights equal to the number of Rights such holder would have
held if, immediately prior to the Distribution Date, all of the shares of Series
D Preferred Stock had been converted into shares of Common Stock at the then
current Conversion Value (as defined in the Certificate of Designations). As
soon as practicable after the Distribution Date (but in any case no later than 5
business days following the Distribution Date), the Rights Agent will send by
first-class, insured, postage prepaid mail, to each record holder of the Series
D Preferred Stock as of the Close of Business on the Distribution Date, one or
more Rights Certificates evidencing the Rights so held. No further Rights shall
attach or be issuable in respect of any shares of Common Stock issued thereafter
upon conversion of any shares of Series D Preferred Stock. In addition,
notwithstanding any of the foregoing, any holder of a Warrant who exercises any
portion of such Warrant after a Distribution Date shall receive, upon exercise
of such Warrant, a number of Rights equal to the number of Rights such holder
would have held in respect of the Warrant Shares (as defined in the Warrant)
issuable upon such exercise if the portion of the Warrant being exercised had
been exercised immediately prior to the Distribution Date. As soon as
practicable after such exercise (but in any case no later than 5 business days
following such exercise), the Rights Agent will send by first-class, insured,
postage prepaid mail, to the record holder of such Warrant Shares, one or more
Rights Certificates evidencing the Rights so held. In an event that an
adjustment in the number of Rights per share of Common Stock has been made
pursuant to Section 11(p) hereof, the Company shall make the necessary and
appropriate rounding adjustments (in accordance with Section 14(a) hereof) so
that Rights Certificates representing only whole numbers of Rights are
distributed and cash is paid in lieu of any fractional Rights.

                            [SIGNATURE PAGE FOLLOWS]
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      IN WITNESS WHEREOF, the Company and the Rights Agent have caused this
amendment to be executed this 23rd day of July, 2003.

                          Spectrum Pharmaceuticals, Inc.

                          By:  /s/ Rajesh C. Shrotriya
                               ------------------------

                          Name:Rajesh C. Shrotriya, M.D.
                               -------------------------

                          Title:Chairman, Chief Executive Officer and President
                                -----------------------------------------------

                          U.S. Stock Transfer Corporation

                          By:  /s/ Richard C. Brown
                               ---------------------

                          Name:Richard C. Brown
                               ----------------

                          Title:Vice President
                                --------------

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