Caffeine Quinolones

In 1993, Fuhr et al. (159) correlated electrostatic and volume descriptors for a series of quinolone antibacterials with their percentage of inhibition effect of caffeine 3-demethylation in CYP1A2. The descriptors were derived with the SYBYL (207) and ALCHEMY II (208) software packages. It was shown that... 

Ciprofloxacin (Cipro, Cipro XR, Proquin XR) [Antibiotic/ Fluoroquinolone] Uses Rx lower resp tract, sinuses, skin skin structure, bone/joints, urinary tract Infxns including prostatitis Action Quinolone antibiotic DNA gyrase Dose Adults. 250-750 mg PO ql2h XR 500-1000 mg PO q24h or 200-400 mg IV ql2h in renal impair Caution [C, /-] Children <18 y Contra Component sensitivity Disp Tabs, susp, inj SE Restlessness, N/V/D, rash, ruptured tendons, T LFTs Interactions T Effects Wf probenecid T effects OF diazepam, theophylline, caffeine, metoprolol, propranolol, phenytoin, warfarin effects W/ antacids, didanosine, Fe salts. Mg, sucralfate, Na bicarbonate,... 

Un, acute exacerbation of chronic bronchitis prophylaxis in transurethral procedures Action Quinolone antibiotic -1- DNA gyrase. Dose 400 mg/d PO X w/ renal insuff, avoid antacids Caution [C, —] Interactions w/ cation-containing products Contra Quinolone all gy, children <18 y,T QT interval, X Disp Tabs SE NA/ /D, abd pain, photosens, Szs, HA, dizziness, tendon rupture, periph al neuropathy, pseudomembranous cohtis, anaphylaxis Interactions t Effects W/ cimetidine, probenecid T effects OF cyclosporine, warfarin, caffeine X effects W/ antacids EMS Monitor ECG for TqT int val, esp in pts taking class lA/III antiarrhythmics monitor ECG and BP for signs of h5 povolemia and electrol5rte disturbances (hypokalemia) d/t D T risk of photosensitivity Rxns OD May cause NA /D, confusion and Szs symptomatic and supportive... 

Quinolone antibiotics Susceptible to inhibition of gastrointestinal absorption. Some Caffeine [P] Ciprofloxacin, enoxacin, pipedemic acid, and to a lesser extent,... 

The interaction between the quinolone antibacterials and CYP1A2 has been studied in some depth for enoxacin and pefloxacin. Both compounds have been shown to inhibit CYPlA2-mediated metabolism of caffeine in vitro (49). This in vitro inhibition translated into a twofold decrease in caffeine clearance by pefloxacin and a sixfold decrease in clearance by enoxacin (50). Because pefloxacin undergoes N-demethylation to norfloxacin (51) and norfloxacin is much more potent as an inhibitor than pefloxacin (50), the observed in vivo interaction seen for pefloxacin may, in part, be due to norfloxacin. Many other quinolone antibacterial agents have been investigated for their interaction with theophylline, and ciprofloxacin has also been shown to have notable inhibitory effects (52). 

Antidepressants selective serotonin reuptake inhibitors, tricyclic antidepressants Antihypertensives felodipine Antibiotics quinolones, isoniazid Bronchodilators albuterol, theophylline Corticosteroids prednisone Dopa agonists levodopa Herbals ma huang, ginseng, ephedra Nonsteroidal anti-inflammatory drugs ibuprofen Stimulants amphetamines, methylphenidate, caffeine, cocaine Sympathomimetics pseudoephedrine Thyroid hormones levothyroxine Toxicity anticholinergics, antihistamines, digoxin Withdrawal alcohol, sedatives... 

The effects of various quinolones on the pharmacokinetics of caffeine " are summarised in Table 33.3 , (p.l 167). In one study ciprofloxacin and fleroxacin increased caffeine levels more in women than men, but this difference in effect was not significant when the results were normalised for body weight. ... 

It would seem that the metabolism (7V-demethylation) of caffeine is markedly reduced by some quinolones (notably pipemidic acid and enoxacin) resulting in greater levels and possibly greater effects. Other quinolones... 

Established interactions. Based on the results of two studies, on a scale of 100 to 0, the relative potencies of these quinolones as inhibitors of caffeine elimination have been determined as follows enoxacin 100, pipemidic acid 29, ciprofloxacin 11, norfloxacin 9 and ofloxacin 0. From further studies, clinafloxacin appears to be similar to enoxacin (profound effect), pefloxacin to norfloxacin (to which it is metabolised modest effect), and fleroxacin, lomefloxacin, rufloxacin, and trovafloxacin appear to behave like ofloxacin (no effect). Patients taking enoxacin might be expected to experience an increase in the effects of caffeine (such as headache, jitteriness, restlessness, insomnia) if, for example, they continue to drink their usual amounts of caffeine-containing drinks (tea, coffee, cola drinks, etc.). They should be warned to cut out or reduce their intake of caffeine if this occurs. The authors of one report suggest that patients with hepatic disorders, cardiac arrhythmias or latent epilepsy should avoid caffeine if they take enoxacin for one week or more. The effects of pipemidic acid arc less, and those of ciprofloxacin, norfloxacin and pefloxacin arc probably of little or no clinical importance. Fleroxacin, lomefloxacin, ofloxacin, rufloxacin, and trovafloxacin do not interact. 

Staib AH, Stille W, Dietlein G, Shah PM, Harder S, Mieke S, Beer C. Interaction between quinolones and caffeine. Drugs (1987) 34 (Siq>pl 1), 17(M. 

Harder S, Staib AH, Beer C, Papenbuig A, Stille W, Shah PM 4-Quinolones inhibit biotrans-formation of caffeine EurJ Clin Pharmacol (1988) 35,651-6. 

Fuhr U, Wolff T, Harder S, Sch3mianski P, Staib AH. Quinolone inhibition of cytochrome P450-dependent caffeine metabolism in human liver microsomes. DrugMetrA Di os (1990) 18,1005-10. 

Barnett G, Segura J, de la Torre R, Carb6 M Pharmacokinetic detennination of relative potency of quinolone inhibition of caffeine disposition. EurJ Clin Pharmacol (1990) 39,63—9. 

Table 33.3 Effect of quinolones on caffeine pharmacokinetics in healthy subjects...

Quinolone Daily caffeine intake Change in AUC Change in clearance Refs... 

Carb6 M, Segura J, De la Torre R, Badenas JM, Cami J. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther (1989) 45, 234-40. 

---