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Associate Professor Bob Milne

Position: Research Degrees Coordinator
Division/Portfolio: Division of Health Sciences
School/Unit: School of Pharmacy and Medical Sciences
Campus: City East Campus
Office: R1-14
Telephone: +61 8 830 22335
Fax: +61 8 830 22389
Email: Robert_dot_Milne_at_unisa_dot_edu_dot_au
URL for Business Card: http://people.unisa.edu.au/Robert.Milne


Welcome to my homepage. I have a number of responsibilities within the School of Pharmacy and Medical Sciences.

I teach courses in Pharmaceutical Science/Dosage Form Design and Pharmacokinetics in the Pharmaceutical Science and Pharmacy programs.

As a member of the Sansom Institute located within the School, I am the leader of the Pharmaceutical science Sector and am actively involved in a number of research projects with staff in the Institute and with colleagues attached to hospitals in Adelaide and interstate.

I consult widely to the pharmaceutical and biotechnology industry on pre-clinical and clinical studies, and work closely with CPR Pharma, a spin-out company from UniSA.

My professional activities include previous executive roles with the Australasian Pharmaceutical Science Association (APSA) and the South Australian Branch of the Pharmaceutical Society of Australia and organization of annual conferences on behalf of both organizations.

I am also the Research Degrees Co-ordinator for the School.


Teaching interests

  • Pharmaceutics (the science behind the design of dosage forms for administering drugs)
  • Pharmacokinetics and Biopharmaceutics (a course which studies the fate of drugs in the body and how long they remain in the body)

I teach the following courses

PHAR 2011Pharmaceutical Science 1
PHAR 2014Dosage Form Design P1
PHAR 2006Pharmacokinetics and Biopharmaceutics P 201
PHAR 2012Pharmaceutical Science 2


Professional associations

International Society for the Study of Xenobiotics

Australasian Pharmaceutical Science Association

Australian Society for Antimicrobials

Malaysian Pharmaceutical Society


Qualifications

B. Pharm. (Hons., Sydney)

M.Sc. (Sydney)

Ph.D. (Adelaide)


Research interests

  • Pharmacokinetics and metabolism of drugs and their metabolites
  • Disposition of drugs and their metabolites in isolated perfused organs
  • Drug analysis
  • Antimicrobial drugs, antianginal drugs, glucuronide metabolites, drug interactions with complementary medicines
  • Microdialysis and tumour uptake of anticancer agents

Research publications

Nation, R.L., Evans, A.M. & Milne, R.W. Pharmacokinetic Drug Interactions with Phenytoin. (Part I) Clin. Pharmacokinet. 18, 37-60 (1990).

Nation, R.L., Evans, A.M. & Milne, R.W. Pharmacokinetic Drug Interactions with Phenytoin. (Part II) Clin. Pharmacokinet. 18, 131-150 (1990).

Milne, R.W., Nation, R.L., Reynolds, G.D. & Somogyi, A.A. Improved method for the determination of morphine and its 3- and 6-glucuronide metabolites. J. Chromatogr. 565, 457-464 (1991).

Sloan, P.A., Mather, L.E., McLean, C.F., Rutten, A.J., Nation, R.L., Milne, R.W., Runciman, W.B. & Somogyi, A.A. Physiological disposition of i.v. morphine in sheep. Brit. J. Anaesth. 67, 378-386 (1991).

Milne, R.W., Nation, R.L., Somogyi, A.A., Bochner, F. & Griggs, W. Effect of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive-care patients. Brit. J. Clin. Pharmacol. 34, 53-59 (1992).

Somogyi, A.A, Nation, R.L., Olweny, C., Tsirgiotis, P., van Crugten, J., Milne, R.W., Cleary, J.F., Danz, C. & Bochner, F. Plasma concentrations and renal clearance of morphine, morphine-3-glucuronide and morphine-6-glucuronide in cancer patients receiving morphine. Clin. Pharmacokin. 24, 413-420 (1993).

Milne, R.W., Sloan, P.A., McLean, C.F., Mather, L.E., Nation, R.L., Runciman, W.B., Rutten, A.J. & Somogyi, A.A. The disposition of morphine and its 3- and 6-glucuronide metabolites during morphine infusion in the sheep. Drug Metab. Dispos. 21,1151-1156 (1993).

Milne, R.W., McLean, C.F., Mather, L.E., Nation, R.L., Runciman, W.B., Rutten, A.J. & Somogyi, A.A. Comparative disposition of morphine-3-glucuronide during separate intravenous infusions of morphine and morphine-3-glucuronide. Drug Metab. Dispos. 23, 334-342 (1995).

Milne, R.W., Nation, R.L. & Somogyi, A.A. The disposition of morphine and its 3- and 6-glucuronide metabolites in humans and animals, and the importance of the metabolites to the pharmacological effects of morphine. Drug Metab. Rev. 28, 345-472 (1996).

Milne, R.W., McLean, C.F., Mather, L.E., Nation, R.L., Runciman, W.B., Rutten, A.J. & Somogyi, A.A. Influence of renal failure on the disposition of morphine, morphine-3-glucuronide and morphine-6-glucuronide in sheep during intravenous infusion with morphine. J.Pharmacol.Exp.Ther. 282, 779-786 (1997).

Milne, R.W., R.H. Jensen, C. Larsen, A.M. Evans & Nation, R.L. Comparison of the disposition of hepatically-generated morphine-3-glucuronide and morphine -6-glucuronide in isolated perfused liver from the guinea pig. Pharm. Res. 14, 1016-1020 (1997).

Stretch, G.L., Nation, R.L., Evans, A.M. & Milne, R.W. Organ perfusion techniques in drug development. Drug Development Research. 46, 292-301 (1999).

Milne, R.W., Larsen, L.A., Jørgensen, K.L., Bastlund, J., Stretch, G.R. and Evans, A.M. Hepatic Disposition of fexofenadine: influence of the transport inhibitors erythromycin and dibromosulphothalein. Pharm. Res. 17, 1511-1515 (2000).

Shackleford, D.M., Hayball, P.J., Reynolds, G.D., Hamon, D.P.G., Evans, A.M., Milne, R.W. and Nation, R.L. A small-scale synthesis and enantiomeric resolution of (RS)-[1-14C]-2-phenylpropionic acid and biosynthesis of its diastereomeric acyl glucuronides. J. Labelled Cpd. Radiopharm. 44, 225-234 (2001).

Li, J., Turnidge, J., Milne, R., Nation, R.L. and Coulthard, K. In vitro pharmacodynamic properties of colistin and colistin methanesulphonate against Pseudomonas aeruginosa isolates from patient with cystic fibrosis. Antimicrob. Agents Chemother. 45, 781-785 (2001).

Li, J., Milne, R.W., Nation, R.L., Turnidge, J. and Coulthard, K. A novel assay method for colistin in human plasma using pre-column derivatization with 9-fluorenylmethyl chloroformate for RP-HPLC. J. Chromatogr. 761/2, 167-175 (2001).

Li, J., Milne, R.W., Nation, R.L., Turnidge, J., Coulthard, K. and Valentine, J. Simple method for assaying colistin methanesulphonate in plasma and urine using high-performance liquid chromatography. Antimicrob. Agents Chemother. 46, 3304-3307 (2002).

Upton, R.N., Ludbrook, G.L., Martinez, A.M., Grant, C., and Milne, R.W. Cerebral and lung kinetics of morphine in conscious sheep after short intravenous infusions. Brit. J. Anaesth. 90, 750-758 (2003).

Li, J., Milne, R.W., Nation, R.L., Turnidge, J. and Coulthard, K. The stability of colistin and colistin methanesulfonate in aqueous media and plasma studied by high-performance liquid chromatography. Antimicrob. Agents Chemother. 47, 1364-1370 (2003).

Lucas, A.N., Nation, R.L., Milne, R.W., Reynolds, G.D. and Evans, A.M. The effects of phytoestrogenic isoflavones on the formation and disposition of paracetamol sulfate in the isolated perfused rat liver. J. Pharm. Pharmacol. 55, 639-646 (2003).

Li, J., Milne, R.W., Nation, R.L., Turnidge, J., Smeaton, T. and Coulthard, K. Use of high-performance liquid chromatography to study the pharmacokinetics of colistin sulfate in rats following intravenous administration. Antimicrob. Agents Chemother. 47, 1766-1770 (2003).

Shackleford, D.M., Nation, R.L., Milne, R.W., Hayball, P.J. & Evans, A.M. Stereoselective hepatic disposition of model diastereomeric acyl glucuronides. J. Pharmacokin. Pharmacodyn., 31, 1-27 (2004).

Bain, M., Faull, R. Fornasini, G., Milne, R.W., Schumann, R. & Evans, A.M. Quantifying trimethylamine and trimethylamine-N-oxide in human plasma: interference from endogenous quaternary ammonium compounds. (Anal. Biochem., 334, 403-405 (2004).

Li. J, Nation, R.L., Milne, R.W., Turnidge, J.D. and Coulthard, K. Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria. Int. J. Antimicrob. Agents, 25, 11-26 (2005).

Wiese, M., Chataway, T.K., Noel W Davies, N.W., Robert W Milne, R.W., Simon G.A. Brown, S.G.A., Gai, W-P & Heddle, R.J. Proteomic analysis of Myrmecia pilosula (Jack Jumper) ant venom. Toxicon 47, 208-217 (2006).

Bain, M., Faull, R., Fornasini, G., Milne, R.W. & Evans, A.M. Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrology Dialysis Transplantation 21, 1300-1304 (2006).

Davies, B.J., Herbert, M.K., Culbert, J.A., Pyke, S.M., Coller, J.K., Somogyi, A.A., Milne, R.W. & Sallustio, B.C. Enantioselective assay for the determination of perhexiline enantiomers in human plasma by liquid chromatography. J. Chromatogr. B. 832, 114-120 (2006).

Li.J., Nation, R.L., Turnidge, J.D., Milne, R.W., Coulthard, K., Rayner, C.R. & Paterson, D.L. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. The Lancet Infectious Diseases 6, 589-601 (2006).

Davies, B.J., Herbert, M.K., Coller, J.K., Somogyi, A.A., Milne, R.W. & Sallustio, B.C. Determination of the 4-monohydroxy metabolites of perhexiline in human plasma, urine and liver microsomes by liquid chromatography. J. Chromatogr. B..843, 302-309 (2006).

Bain, M., Milne, R.W. & Evans, A.M. Disposition and metabolite kinetics of oral L-carnitine in humans. J. Clin. Pharmacol. 46, 1163-1170 (2006).

Shackleford, D.M., Evans, A.M., Milne, R.W. &. Nation, R.L. Loading-washout studies of the stereoselective sinusoidal uptake of (R)- and (S)-2-phenylpropionyl acyl glucuronide. Curr. Drug Metab. 7, 817-826 (2006).

Bain, M., Faull, R., Milne, R.W. & Evans, A.M. Oral L-carnitine: metabolite formation and hemodialysis. Curr. Drug Metabolism 7, 811-816 (2006).

Davies, B.J., Herbert, M.K., Coller, J.K., Somogyi, A.A., Milne, R.W. & Sallustio, B.C. Determination of the 4-monohydroxy metabolites of perhexiline in human plasma, urine and liver microsomes by liquid chromatography. J. Chromatogr. B..843, 302-309 (2006).

Ma, J., Ma, Z., Wang, J., Milne, R.W., Xu, D., Davey, A.K. & Evans, A.M. Isosteviol reduces plasma glucose levels in the intravenous glucose tolerance test in Zucker diabetic fatty rats. Diabetes Obes. Metab. 9, 597-599 (2007).

Inglis, S.C., Herbert, M.K., Davies, B.J.L, Coller, J.K., James, H.M., Horowitz, J.D., Morris, R.G., Milne, R.W., Somogyi, A.A. & Sallustio, B.C. Effect of CYP2D6 metaboliser status on the disposition of the (+)- and (-)-enantiomers of perhexiline in patients with myocardial ischaemia. Pharmacogenetics & Genomics 17, 305-312 (2007)

Davies, B.J., Coller, J.K., Somogyi, A.A., Milne, R.W. & Sallustio, B.C. CYP2B6, CYP2D6 and CYP3A4 catalyse the primary oxidative metabolism of perhexiline enantiomers by human liver Drug Metab. Dispos. 35, 128-138 (2007).

Wiese, M.D., Brown, S.G.A., Chataway, T.K., Davies, N.W., Milne, R.W., Aulfrey, S.J. & Heddle, R.J. Myrmecia pilosula (Jack Jumper) an venom: identification of allergens and revised nomenclature. Allergy 62, 437 – 443 (2007)

McLachlan, A.J., Ramzan, I. & Milne, R.W. Frequently asked questions about generic drugs. Australian Prescriber 30, 41 - 43 (2007).

Davies, B.J., Herbert, M.K., Coller, J.K., Somogyi, A.A., Milne, R.W. & Sallustio, B.C. Steady-state pharmacokinetics of the enantiomers of perhexiline in CYP2D6 poor and extensive metabolisers administered rac-perhexiline. Brit. J. Clin. Pharmacol. 65, 347 – 354 (2008)

Wiese, M.D., Milne, R.W., Davies, N.W., Chataway, T.K, Brown, S.G.A. & Heddle, R.J. Myrmecia pilosula (Jack Jumper) Ant Venom: Validation of a procedure to standardise an allergy vaccine. J. Pharm. Biomed. Anal. 46, 58-65 (2008)

Ma, Z., Wang, J., Gerber, C. & Milne, R.W. Determination of colistin in human plasma, urine and other biological samples, J. Chromatogr. B. 862, 205 – 212 (2008)

Bergen, P.J., Li, J., Nation, R.L., Turnidge, J.D., Coulthard, K. & Milne, R.W. Comparison of once-, twice and thrice-daily dosing of colistin on antibacterial effect and emergence of resistance: studies with Pseudomonas aeruginosa in an in vitro pharmacodynamic model. J. Antimicrob. Chemother. 61, 636 – 642 (2008)

Wallace, S.J., Li, J., Nation, R.L., Rayner, C.R., Taylor, D., Middleton, D., Milne, R.W., Coulthard, K & Turnidge, J.D. Sub-acute toxicity of colistin methanesulfonate in rats: comparison of various intravenous dosage regimens. Antimicrob. Agents Chemother. 52: 1159-1161 (2008)

Ma, Z., Wang, J., Nation, R.L., Li, J., Turnidge, J.D., Coulthard, K. & Milne, R.W. Renal disposition of colistin in the isolated perfused kidney. Antimicrob. Agents Chemother. 53, 2957-2864 (2009).

Turkanovic, J., Ngo, S.N.T. & Milne, R.W. Effect of St. John’s wort on the disposition of fexofenadine in the isolated perfused rat liver. J. Pharm. Pharmacol. 61, 1037 – 1042 (2009)


Research Degree Supervisor

Currently, my focus is on three major projects:

The first project is examining the pharmacokinetics and pharmacodynamics of colistin and its methanesulphonate derivative. This is an old antibiotic for which there is renewed interest in its value for treating infections caused by multi-resistant Pseudomonas aeruginosa and other gram negative microorganisms. Unfortunately, its use is limited by the lack of useful data. We have examined its pharmacokinetics in humans and animals, and its in vitro activity, but wish to pursue further work on its pharmacodynamics and toxicity so that appropriate dosage regimens can be designed. Our group is a world leader in research with this antibiotic.

The second project is examining the pharmacokinetics and pharmacodynamics of perhexiline, once again an old drug for which there is an increasing appreciation of its value for treating angina as better information becomes available that will allow it to be used with greater safety. This is one of the last line of drugs available for treating patients with refractory angina. However, prescribers are often concerned about the risks of hepatotoxicity and neurotoxicity. A better understanding of the fate of this drug in humans and the relative activity of its enantiomers towards relieving angina and causing toxicity will provide greater confidence in its use by medical practitioners.

The third project with which I am involved is a collaboration between Professor Allan Evans and myself in developing microdialysis methods for examining the disposition of drugs in plasma and tissues. Currently, the method is being used to examine anticancer drugs, their uptake into tumour tissue, and ways of increasing specificity in the delivery of these drugs to the tissue.





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