Penicillin distribution

Penicillin is produced by fermentation and recovered from the resulting aqueous broth by extraction with butyl acetate. The penicillin distribution coefficient K (mass fraction of penicillin in the butyl acetate phase/mass fraction of penicillin in the water phase) depends strongly on the pH in the aqueous phase ... 

Being weak acids with a pfCg of 2.7, penicillins have low values (typically 0.2-0.31/kg). After absorption, penicillins distribute mainly into the ECF. CSF concentrations are 10% of plasma concentrations unless the meninges are inflamed. Penicillins distribute into milk but reach only subtherapeutic concentrations for most bacteria. Penicillins cross the placenta but are not associated with producing adverse effects in the fetus. Protein binding is considered to be moderate (52-54%). 

The article translated by H. Umezawa, with other related papers, was widely distributed to many universities and institutes, and this, with the establishment of the Penicillin Committee, opened the door for antibiotics in Japan. Hamao s premonition that microbes would be a mysterious box, full of hitherto unknown and valuable compounds, was very exciting. He was dissatisfied with the Japanese medical world at the time, which laid emphasis on the diagnosis and elucidation of diseases, but not on effective cure of patients having, for example, tuberculosis. 

Cephalosporins. These beta-lactam antibiotics share many features with the penicillins including mechanism, spectrum of action, distribution ans toxicity potential. At the present time, the cephalosporins are classified into three groups, designated as generations. 

Distribution - Penicillins are bound to plasma proteins, primarily albumin, in varying degrees. They diffuse readily into most body tissues and fluids. 

Probenecid can impair the renal active secretion of a variety of acidic compounds, including sulfinpyrazone, sulfonylureas, indomethacin, penicillin, sulfonamides, and 17-ketosteroids. If these agents are to be given concomitantly with probenecid, their dosage should be modified appropriately. Salicylates interfere with the clinical effects of both sulfinpyrazone and probenecid and should be avoided in patients treated with uricosuric agents. Uricosuric agents also can influence the volume of distribution and hepatic metabolism of a number of drugs. 

Penicillin G (benzylpenicillin) is an acid-labile compound having variable bioavailability after oral administration. Consequently, penicillin G is most appropriate for intramuscular or intravenous therapy. The drug distributes to most tissues and serosa-lined cavities, although low concentrations appear in breast milk and... 

Mezlocillin, piperacillin, and ticarcillin are parenteral antibiotics formulated as sodium salts, so prescribers must consider the sodium content of these antibiotics when administering them to patients with congestive heart failure. During their distribution phase, antipseudomonal penicillins achieve orfly low concentrations in the cerebrospinal fluid. Consequently, antipseudomonal penicillins are not among the drugs of first choice for meningitis therapy. 

Mechanism of Action A fixed-combination carbapenem. Imipenem penetrates the bacterial cell membrane and binds to penicillin-binding proteins, inhibiting cell wall synthesis. Cilastatin competitively inhibits the enzyme dehydropeptidase, preventing renal metabolism of imipenem. Therapeutic Effect Produces bacterial cell death. Pharmacokinetics Readily absorbed after IM administration. Protein binding 13%-21%. Widely distributed. Metabolized in the kidneys. Primarilyexcreted in urine. Removed by hemodialysis. Half-life 1 hr (increased in impaired renal function). 

Pharmacokinetics Penicillins are generally well absorbed from the gastrointestinal (GI) tract after oral administration. Widely distributed to most tissues and body fluids. Protein binding 20%. Partially metabolized in liver. Primarily excreted in urine. Half-life varies (half-life increased in reduced renal function). 

Schugerl 115] has recently furnished a detail analysis of the reactive extraction of penicdlin-G and V and precursors like phenyl and phenoxy acetic acids. Thirty different amines have been studied for reactive extraction of penicillins 116] in various solvents such as butyl acetate, chloroform, di-isopropyl ether, kerosene, dioctyl ether, etc. Tertiary amines in n-butyl acetate were found to be advantageous because of their low reactivity with solvent but the distribution coefficients of their complexes are significantly lower than those of secondary amines. While using quaternary ammonium salts for ion-exchange extraction, re-extraction is difficult and very large amounts of anion (e.g.. Cl ) are needed to recover penicillins. The basic relationship for distribution coefficient and extraction kinetics have now been fairly developed for amine-penicillin systems. 

After oral administration, benzyl penicillin is destroyed by gastric acid. It is mainly absorbed from the duodenum. It is absorbed in aqueous solution rapidly after intramuscular or subcutaneous administration. Penicillin is widely distributed in the body after absorption and approximately 60% of plasma penicillin is bound to albumin. The major... 

Cephalosporins are distributed in the body after oral or parenteral administration in same manner as penicillin is distributed. The majority are not metabolized and are eliminated by kidney. 

Distribution of penicillin antibiotics is limited to extracellular fluids, but inflammation may enhance their distribution into tissues. Penicillins are actively transported in kidney, brain, and liver. Most penicillins undergo minimal hepatic metabolism and are cleared from the plasma primarily by renal excretion. Secretion of penicillins by the renal tubules results in high urine concentrations and rapid elimination from the body (50). 

Structure—Activity Relationships. Biological evaluation of penicillins yields information such as in vitro and in vivo antibacterial activities, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), protective effectiveness in laboratory animals (PD50), and pharmacokinetic characteristics including efficiency of absorption, serum levels, tissue distribution, urinary excretion, recycling, etc. Penicillins are also tested for ability to resist inactivation by (S-lactamase produced by both gram-positive and gram-negative bacteria,... 

---