City of Fairfield, Independent Auditor's Report, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

City Audit Report

Grundy County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Montgomery County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

County Audit Report

Lee County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

City of Central City, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2003 & June 30, 2004

City Audit Report

5B Judicial District Youth Services, Independent Auditor's Reports, Basic Financial Statements, Schedule of Findings, Eight Months ended February 28, 2005 and Year ended June 30, 2004

Other Audit Reports - 28E Organizations

5B Judicial District Youth Services, Independent Auditor's Reports, Basic Financial Statements, Schedule of Findings, Eight months ended February 28, 2005 and Year Ended June 30, 2004

Other Audit Reports - 28E Organizations

Jasper County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings and Questioned Costs, June 30, 2004

County Audit Report

Dickinson County, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2004

County Audit Report

Fremont County Landfill Commission, Independent Auditor's Reports, Basic Finacial Statements and Required Supplementary Information, Schedule of Findings, June 30, 2004

Other Audit Reports - 28E Organizations

Iowa Federal Family Education Loan Program Division, Iowa College Student Aid Commission, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, June 30, 2004

State Audit Reports

City of Carter Lake, Independent Auditor's Reports, Basic Financial Statements and Supplementary Information, Schedule of Findings, June 30, 2005

City Audit Report

City of Donnellson Independent Auditor's Report Basic Finanical Statements and Supplementary Information Schedule of Findings, June 30, 2004

Independent Auditor's Reports, Basic Financial Statements, Supplementary Information and Schedule of Findings

Binding of amitriptyline to alpha 1-acid glycoprotein and its variants.

Binding studies have been performed between amitriptyline and i) native alpha 1-acid glycoprotein (AAG); ii) its desialylated form; iii) its two variants, S-AAG and F-AAG; and iv) a mixture of S-AAG and F-AAG. Scatchard analysis revealed the presence of two classes of binding sites on AAG. For native AAG, the first class (of high affinity) has an association constant (Ka1) of 1.5 x 10(6) L mol-1 and a number of binding sites per mole of protein (n1) of 0.25, while the second class (of low affinity) has a Ka2 of 3.2 x 10(4) L mol-1 and a n2 of 0.94. Similar data were found for desialylated AAG. S-AAG and F-AAG do not differ in their association constants measured with amitriptyline, but in their number of binding sites per mole of protein (n): S-AAG: n1 = 0.56, n2 = 0.52; F-AAG: n1 = 0.17, n2 = 0.71. These results confirm those of a previous study, in which a higher affinity of S-AAG towards various basic drugs in comparison with F-AAG has been found.

Population PK-guided simulation study in children exposed to drugs in human milk

Risks of significant infant drug exposure through human milk arepoorly defined due to lack of large-scale PK data. We propose to useBayesian approach based on population PK (popPK)-guided modelingand simulation for risk prediction. As a proof-of-principle study, weexploited fluoxetine milk concentration data from 25 women. popPKparameters including milk-to-plasma ratio (MP ratio) were estimatedfrom the best model. The dose of fluoxetine the breastfed infant wouldreceive through mother's milk, and infant plasma concentrations wereestimated from 1000 simulated mother-infant pairs, using randomassignment of feeding times and milk volume. A conservative estimateof CYP2D6 activity of 20% of the allometrically-adjusted adult valuewas assumed. Derived model parameters, including MP ratio were consistentwith those reported in the literature. Visual predictive check andother model diagnostics showed no signs of model misspecifications.The model simulation predicted that infant exposure levels to fluoxetinevia mother's milk were below 10% of weight-adjusted maternal therapeuticdoses in >99% of simulated infants. Predicted median ratio ofinfant-mother serum levels at steady state was 0.093 (range 0.033-0.31),consistent with literature reported values (mean=0.07; range 0-0.59).Predicted incidence of relatively high infant-mother ratio (>0.2) ofsteady-state serum fluoxetine concentrations was <1.3%. Overall, ourpredictions are consistent with clinical observations. Our approach maybe valid for other drugs, allowing in silico prediction of infant drugexposure risks through human milk. We will discuss application of thisapproach to another drug used in lactating women.