Testosterone Warfarin

Fig. 3. Relationship between substrate lipophilicity (log P) and ability of screened microorganisms to metabolize model substrates (AP = Aminopyrine DZ = Diazepam TE = Testosterone TH = Theophylline WF = Warfarin). Log P is the logarithm of the partition coefficient of a compound between n-octanol and a pH 7.0 aqueous buffer. Ordinates represent the % of cultures tested able to transform the substrates, independently of the extent of metabolism and number of products formed (from [185])...

A4 Nifedipine, ethylmorphine, warfarin, quinidine, taxol, ketoconazole, verapamil, erythromycin, diazepam Aflatoxin, 1-nitropyrene, benzo(a)pyrene 7,8-diol, 6 aminochrysene, estradiol, progesterone, testosterone, other steroids, bile acids Erythromycin, nifedipine [testosterone (6-/3)]... 

Fig. 4.1 Correlation of permeability and total hydrogen-bonding capacity for a series of structural heterogeneous compounds corticosterone (Co), testosterone (Te), propranolol (Pr), alprenolol (Al), warfarin (Wa), metoprolol (Me), felodipine (Fe), hydrocortisone (Hy),...

Studies have shown that gastrointestinal mucus presents a physical barrier to the diffusion of small molecules such as urea, benzoic acid, antipyrine, 1-phenylalanine and warfarin as well as to large protein molecules. Similarly, the passive absorption of testosterone was shown to be doubled upon ridding the intestinal epithelial cells of the overlying mucus layer. However, the situation regarding the effect of mucus on oral bioavailability is a complex one for example, it has been shown that drag binding to the mucosal surface is essential to the absorption of barbituric acid derivatives from the rat small intestine. 

It is instructive to examine which drugs are substrates for various isoforms of CYP enzymes. Table 11.2 lists some of the substrates for different CYP isoforms (10, 11). There are several examples of a single compound that is metabolized by multiple CYP enzymes (acetaminophen, diazepam, caffeine, halothane, warfarin, testosterone, zidovudine), and CYP enzymes that metabolize bioactive endogenous molecules (prostaglandins, steroids) as well as drugs. 

A4 34.1 Acetaminophen, caffeine carbamazepine, codeine, cortisol, erythromycin, cyclophosphamide, (S)-and (R)-warfarin, phenytoin, testosterone, halothane, zidovudine... 

Prednisolone Progesterone Protease Inlaibitors Quinidine (1 )-Warfarin Rifampin Sertraline Sirolimus Simvastatin Tacrolimus Testosterone Trazadone Triazolam Voriconazole ... 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Figure 17.4 Compounds which are mentioned throughtout the chapter and numbered in the main text as follows (1) DMZ, (2) diclofenac, (3) flurbiprofen, (4) warfarin, (5) fluconazole, (6) coumarin, (7) dapsone, (8) retinoic acid, (9) arachidonic acid, (10) troglitazone, (11) fluvastatin, (12) cerivastatin, (13) taxol, (14) gemfibrozil, (15) verapamil, (16) amodiaquine, (17) amiodarone, (18) metyrapone, (19) progesterone, (20) testosterone, (21) erythromycin, (22) ketoconazole, (23) nicotine, (24) IV -Nitrosonor-nicotine, (25) 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone...

Arachidonic acid, benzo[a]pyrene, carbamazepine, clozapine, cyclophosphamide, S) and (R)-ibuprofen, omeprazole, paclitaxel, progesterone, retinoic acid, sulfadiazine, temazepam, testosterone, tienilic acid, trimethoprim, (J2)-warfarin, zidovudine Sulfafenazole Rifampicin... 

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