Naproxen Captopril

The different aspects of drug targeting using LMWPs that have been studied to date are discussed below. As an example, we use the data of two conjugates, naproxen-lysozyme and captopril-lysozyme. 

Figure 5.9. The concentration-time course of (a) naproxen and (b) captopril in the kidney after intravenous injection of the parent drug or the drug-lysozyme (LZM) conjugate. Values are given as means + SEM.

A spacer was used to link captopril via a disulfide bond to the LMWP lysozyme. Conjugation of captopril to lysoz5me resulted in a 6-fold increase in captopril accumulation in the rat kidney (Eigure 5.9b) [77]. This modest enrichment, as compared to that achieved with naproxen-lysozyme, was due to fact that, in contrast to naproxen, free captopril is cleared very efficiently by the kidney itself. Thus, delivery via lysozyme reabsorption only leads to a limited improvement of renal accumulation of captopril. 

Sotalol, metoprolol, propranolol, carvedilol, nifedipine, captopril, cilazapril, milrinone, ticlopidine, acenocoumarol, furosemide, acetylsalicylic acid, salicylic acid, ibuprofen, naproxen, ketoprofen, diclofenac, paracetamol, dipyrone, mildronate, sildenafil, dexa-methasone, carbamazepine, terbinafine/urine UHPLC MS/MS Column Zorbax Rapid Resolution High Definition SB-C18 (50 x 2.1 mm, 1.8 pm) Mobile phase Solvent A 0.1 % HCOOH in water Solvent B MeOH (gradient elution) Detection MS/MS, ionization ESI Protein precipitation LOQ 0.05-0.60 ng/mL [71]... 

The manufacture of fine chemicals, particularly drugs, fragrances, and flavors, is undergoing a major revolution now as a result of the capability of chemists to prepare these chemicals, mainly drugs, in their purest isomeric forms (as stereoisomers). This shift to pure forms has been described by Brown in the following words (1990) (see also Deutsch, 1991) A mixture of stereoisomers in a medicine will (now) need to be justified just the same way as any other mixture of compounds. Indeed, in the United States today (as in many other advanced countries), the use of pure enantiomeric forms is practically a requirement since extensive justification is needed to continue with racemates (FDA, 1992). As a consequence, the combined sales of the chiral top ten drugs (ammoxydllin, enalapril, ampicillin, captopril, pravastatine, diltiazem, ibuprofen, lovastatin, naproxen, and fluoxetine) in 1994 amounted to more than 16 billion dollars (Sheldon, 1996). (Of these, ibuprofen and fluoxetine are still sold as racemates.)... 

Types of chiral processes amenable to scale-up Specific examples of the manufacture of chiral drugs Diltiazem Captopril Enalapril Naproxen... 

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