Pharmacology: Pharmacodynamics: Polymyxin B Sulfate is a mixture of polymyxins B1 and B2, obtained from Bacillus polymyxa strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for infections with gram-negative organisms, but may be neurotoxic and nephrotoxic. All gram-positive bacteria, fungi, and the gram-negative cocci, N. gonorrhea and N. meningitides, are resistant.
Pharmacokinetics: Polymyxin B Sulfate is not absorbed from the normal alimentary tract. Since the drug loses 50 percent of its activity in the presence of serum, active blood levels are low. Repeated injections may give a cumulative effect. Levels tend to be higher in infants and children. The drug is excreted slowly by the kidneys. Tissue diffusion is poor and the drug does not pass the blood brain barrier into the cerebrospinal fluid. In therapeutic dosage, Polymyxin B sulfate causes some nephrotoxicity with tubule damage to a slight degree.
Polymyxin B is administered as its sulfate salt which is the active antibiotic. Thus conversion is not required. It is eliminated mainly non-rental pathways. As a result, Polymyxin B concentration in the urine is low. The total body clearance appears to be relatively insensitive to renal function. Inter-individual variability in plasma concentration is low. Its serum half-life depends on the age of the patient and ranges from 3.1 (in neonates) to 13.6 hours. The unbound fraction in plasma is approximately 40%. A loading does not seems to improve significantly its PK parameters.
Pharmacokinetic - Pharmacodynamics relationship: Tissue binding is a dominant factor in the distribution and elimination of polymyxins. Old experimental studies have shown that polymyxins accumulate in liver, lung, kidney, heart, and muscles. At 24h, less than 50% of the doses of Polymyxins were bound to tissues; the largest amount was in the skeletal muscle.