Primaxin - Imipenem

Chemical synthesis Primaxin Imipenem cilastatin 398 Merck... 

There are two additional important variations on the theme of p-lactam antibiotics. These are the carbapenems, of which imipenem (Primaxin) is the outstanding example, and the monobactams, of which aztreonam (Azactam) is the outstanding example (see figure 23.2). 

Imipenem (Primaxin) Indapamide (Lozol) Indinavir (Crixivan)... 

Parenteral 1 g powder to reconstitute for IV (0.9% diluent) or IM (1% lidocaine diluent) injection Imipenem/cilastatin (Primaxin)... 

In humans, imipenem was foimd to be metabolized by an enzyme in the kidney, renal dehydropeptidase-I, which acts as a P-lactamase. Since the enzyme appears to serve no essential role in human metabolism, scientists were able to develop a synthetic competitive inhibitor, cilastatin, which they then used with imipenem to produce the combination drug, primaxin (Tienam). Primaxin was introduced into medical practice in 1985. 

Imipenem (t/ 1 h) is inactivated by metabolism in the kidney to products that are potentially toxic to renal tubules combining imipenem with cilastatin (as Primaxin), a specific inhibitor of... 

Primaxin cilastatin imipenem. primidolol [ban, inn, usan] is a -adrenoceptor antagonist with antihypertensive, antiarrhythmic and antianginal properties, primidone [ban, inn, usan] (Mysoline ) is a pyrimidinedione closely related to the barbiturates, and its actions are similar to phenobarbitone. It is an anticonvulsant that can be used in oral antiepileptic treatment of all forms of epilepsy (except absence seizures) and of essential tremor. 

Extensive carbapenem and penem antibiotic research has been ongoing since thienamycin was discovered in 1978. However, only the imipenem-cilastatin combination has become a commercial product. Launched in 1985 in the United States as a broad-spectrum hospital product under the name Primaxin, this product had woddwide sales of some 300 million in 1988. Sales were predicted to rise to 345 million for the year ending 1989 (154). 

Primaxin IV powder for injection 250 mg imipenem equivalent and 250 mg cilastatin equivalent)... 

Sodium salt, CggH N NaOgS, cilastatin sodium. Off-white to yellowish-white hygroscopic, amorphous solid. pKa, 2.0 pKa2 4.4 pKa, 9.2. Very sol in water, methanol. Combination with imipenem Primaxin, Zienam. 

Imipenem is hydrolyzed by a dipeptidase found in the brush border of the proximal tubule. To prolong drug activity, imipenem is combined with cilastatin, an inhibitor of the dehydropeptidase the combined formulation is available as primaxin. Both imipenem and cilastatin have a t 2 of 1 hour. When administered with cilastatin, 70% of administered imipenem is recovered in the urine as the active drug. Dosage should be reduced for patients with renal insufficiency. 

Forsyth R. Ip D. Determination of imipenem and cilastatin sodium in Primaxin by first... 

Cilastatin - a bulk active pharmaceutical. Merck Co produce an antibiotic Primaxin (cilastatin (22) + imipenem (6)). To produce cilastatin, a process using methylene chloride was used. Methylene chloride features on the US Toxic Release Inventory (TRI) and elimination of emissions from chemical processes has become a priority. Merck have developed a novel process avoiding the use of methylene chloride altogether [13]. The new process, which cost some US 34 million to implement, required a further expenditure of some US 5 million on a fume stripper and US 500 000 on a waste water stripper. However, they claim to have cut their total TRI air emissions by more than 160 tonnes, of which 150 tonnes would have been methylene chloride. Merck also claim that the economics of the new process saved some US 7.2 million during the second half of 1992 alone. 

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