Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

No description available.

No description available.

No description available.

by Wong Yin Kwan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 105-115). / Abstract also in Chinese. / Title page --- p.i / Acknowledgements --- p.ii / Table of contents --- p.iii / Abbreviations --- p.v / Abstract --- p.vi / 摘要 --- p.xi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Assay Development for Ciprofloxacin / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- HPLC Assay --- p.24 / Chapter 2.3 --- Microbiological Assay --- p.29 / Chapter 2.4 --- Discussion --- p.30 / Chapter Chapter 3 --- The Effects of Oral Ferrous Sulfate on Pharmacokinetics and Pharmacodynamics of Intravenous Ciprofloxacin / Chapter 3.1 --- Introduction --- p.43 / Chapter 3.2 --- Materials and Methods --- p.45 / Chapter 3.3 --- Results --- p.49 / Chapter 3.4 --- Discussion --- p.51 / Chapter Chapter 4 --- The Effects of Oral Ferrous Sulfate on Pharmacokinetics and Pharmacodynamics of Oral Ciprofloxacin / Chapter 4.1 --- Introduction --- p.61 / Chapter 4.2 --- Materials and Methods --- p.62 / Chapter 4.3 --- Results --- p.66 / Chapter 4.4 --- Discussion --- p.68 / Chapter Chapter 5 --- Influence of Mineral Rich Traditional Chinese Medicines on the Pharmacokinetics of Oral Ciprofloxacin / Chapter 5.1 --- Introduction --- p.77 / Chapter 5.2 --- Materials and Methods --- p.81 / Chapter 5.3 --- Results --- p.85 / Chapter 5.4 --- Discussion --- p.86 / Chapter Chapter 6 --- General Conclusion --- p.98 / References --- p.105

Chan Siu Lung. / "June 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 220-247). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese,

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

To determine the structure(s) of the spermidine conjugate excreted into urine, extensive pharmacokinetic studies on the turnover of [¹⁴C]spermidine were conducted in both rats and humans. These studies demonstrated that exogenously administered [¹⁴C]spermidine equilibrated with endogenous polyamine pools. Radiolabeled urine collected from the humans was subjected to a cleanup protocol and subsequent analysis by GC-MS, which demonstrated the presence of N-acetylspermidine. Further analysis of the radiolabeled urine by thin layer chromatography (TLC) demonstrated the presence of both N¹- and N⁸-acetylspermidine in an approximate 1 to 1 ratio. Using similar methodologies the monoacetyl derivatives of putrescine and cadaverine were found to be the primary conjugated products of these polyamines excreted into human urine. Radiolabeled rat tissue extracts, analyzed by TLC, demonstrated that all tissues studied contained [¹⁴C] N¹- and N⁸-acetylspermidine. N¹-acetylspermidine was the primary isomer detected in all tissues; although, N⁸-acetylspermidine was detected in all tissues studied. The N-acetylspermidine content of an isolated cell system was determined in Chinese hamster ovary cells. These cells contained both N¹- and N⁸-acetylspermidine in an approximate 2 to 1 ratio. To directly measure the N-acetylpolyamines excreted into urine, two high performance liquid chromatography (HPLC) methods were developed. Both HPLC methods utilize a cation exchange resin, one using high pH, low salt buffers and the other low pH and high salt buffers. The primary N-acetylpolyamine excreted into human urine is N-acetylputrescine with lesser amounts of N¹- and N⁸-acetylspermidine which exist in a 1 to 1 ratio. In contrast, cancer patients excreted elevated amounts of both N-acetylputrescine and N¹-acetylspermidine. Cystic fibrosis patients were also found to excrete elevated amounts of N¹-acetylspermidine resulting in a consistently elevated N¹- to N⁸-acetylspermidine ratio. Mice injected with P-388 leukemia tumor excreted elevated amounts of N-acetylputrescine, N¹-acetylspermidine and N⁸-acetylspermidine. In contrast, the excretion of the unconjugated polyamines putrescine and spermidine in these animals was decreased, suggesting that the altered polyamine excretion was not primarily due to the presence of the tumor. Administration of Adriamycin to the tumor bearing animals resulted in the elevation of N¹-acetylspermidine excretion which was proportional to the relative tumor burden. Similar results were obtained from 2 human leukemia patients studied following chemotherapy.

Part I. The disposition kinetics of 5-fluorouracil (5-FU) and a 5-FU prodrug, 5'-deoxy-5-fluorouridine (5'dFUR), were investigated in twelve patients with colorectal carcinoma. Each patient randomly received either two single, intravenous (iv) doses of 5-FU (7.5 and 15 mg/kg) or 5'dFUR (2 and 4 g/m²) on separate days. In addition, the whole blood/plasma concentration ratio and stability of 5-FU and 5'dFUR at 37°C was determined in whole blood from normal volunteers and in five patients with colorectal carcinoma. A disproportionate increase in area under the curve and corresponding decrease in total body clearance with increasing dose was observed suggesting dose-dependent behavior of both 5-FU and 5'dFUR. The renal clearance of both compounds was independent of dose. Therefore, the mechanism for dose-dependence appears to be primarily due to nonlinear elimination associated with nonrenal processes. The mean 5-FU half-life following the high dose was nearly twice as long as that observed for the low dose suggesting product-inhibition as a possible explanation for the observed nonlinearity in 5-FU elimination. The present studies demonstrate that both 5-FU and 5'dFUR degrade when incubated in whole blood. However, the estimated whole blood clearance does not contribute significantly to the observed total body clearance values. Part II. This investigation examined the influence of gender and cigarette smoking on the disposition of propranolol (P) and metoprolol (M) after both oral and iv administration to twenty healthy volunteers. The only significant differences between smokers and nonsmokers were a higher total body clearance of P and a larger volume of distribution of M in smokers. A comparison of oral clearance values demonstrated that smokers and nonsmokers had a similar capacity to metabolize P and M. Differences between males and females were not observed for any of the pharmacokinetic parameters examined. Nonlinearity in the absorption of P and M was observed and the data suggest marked intersubject differences in the ability of the liver to extract or metabolize these drugs on their first-pass through the liver.