部份中文己酮可可碱处方资料（仅限供参考）
【分类】血管扩张药
【别名】活脑灵；己酮可可豆碱，己酮可可碱，丁咯地尔，己酮可可碱，潘通，循能泰
【外文名】Pentoxifylline，Trental，Pentomer，PentoxifyllineOxpentifylline
【适应症】
用于血栓闭塞性脉管炎、脑血管障碍、血管性头痛等。脑部供血不足(脑部血管硬化/栓塞、老年痴呆症)，末梢血管病、Raynaud氏病、耳蜗扰乱症、冻疮及缺氧所产生的痛症。
【用量用法】
①口服：1次200～600mg，1日3次。静注：1次100～200mg，需缓慢。静滴：每日100～400mg，溶于250～500ml的5%葡萄糖液中，滴注90～180分钟。
②片剂450-600mg/日，分2-3次服用，注射液50-200mg/日，静脉或肌肉注射，静滴。
【注意事项】
1.少数病人服后有胃部不适、恶心、头昏等不良反应。
2.新近心肌梗塞、严重冠状动脉硬化并有高血压者禁用。
3.孕妇不宜使用。
4.个别病人发生视力模糊，过敏性皮疹和皮肤瘙痒等，对肝脏、血象也有影响。5.肝脏疾病患者慎用。
【禁忌】急性脑溢血、严重动脉出血患者，妊娠及哺乳妇女。
【规格】
①片剂：每片100mg。注射液：每支100mg(5ml)。
②片剂150mgx30片。300mgx20片。注射液50mg/5mlx5支。
包装规格[美国包装]
400mg*100tablets/bottles

TRENTAL-pentoxifylline tablet, film coated 
sanofi-aventis U.S. LLC
TRENTAL® (pentoxifylline)Tablets, 400 mg
DESCRIPTION
TRENTAL® (pentoxifylline) tablets for oral administration contain 400 mg of the active drug and the following inactive ingredients: FD&C Red No. 3, hypromellose USP, magnesium stearate NF, polyethylene glycol NF, povidone USP, talc USP, titanium dioxide USP, and hydroxyethyl cellulose USP in an extended-release formulation. TRENTAL is a tri-substituted xanthine derivative designated chemically as 1-(5-oxohexyl)-3,7-dimethylxanthine that, unlike theophylline, is a hemorrheologic agent, i.e. an agent that affects blood viscosity. Pentoxifylline is soluble in water and ethanol, and sparingly soluble in toluene. The CAS Registry Number is 6493-05-6.
The chemical structure is:

CLINICAL PHARMACOLOGY
Mode of Action
Pentoxifylline and its metabolites improve the flow properties of blood by decreasing its viscosity. In patients with chronic peripheral arterial disease, this increases blood flow to the affected microcirculation and enhances tissue oxygenation. The precise mode of action of pentoxifylline and the sequence of events leading to clinical improvement are still to be defined. Pentoxifylline administration has been shown to produce dose-related hemorrheologic effects, lowering blood viscosity, and improving erythrocyte flexibility. Leukocyte properties of hemorrheologic importance have been modified in animal and in vitro human studies. Pentoxifylline has been shown to increase leukocyte deformability and to inhibit neutrophil adhesion and activation. Tissue oxygen levels have been shown to be significantly increased by therapeutic doses of pentoxifylline in patients with peripheral arterial disease.
Pharmacokinetics and Metabolism
After oral administration in aqueous solution pentoxifylline is almost completely absorbed. It undergoes a first-pass effect and the various metabolites appear in plasma very soon after dosing. Peak plasma levels of the parent compound and its metabolites are reached within 1 hour. The major metabolites are Metabolite l (1-[5-hydroxyhexyl]-3,7-dimethylxanthine) and Metabolite V (1-[3-carboxypropyl]-3,7-dimethylxanthine), and plasma levels of these metabolites are 5 and 8 times greater, respectively, than pentoxifylline.
Following oral administration of aqueous solutions containing 100 to 400 mg of pentoxifylline, the pharmacokinetics of the parent compound and Metabolite l are dose-related and not proportional (non-linear), with half-life and area under the blood-level time curve (AUC) increasing with dose. The elimination kinetics of Metabolite V are not dose-dependent. The apparent plasma half-life of pentoxifylline varies from 0.4 to 0.8 hours and the apparent plasma half-lives of its metabolites vary from 1 to 1.6 hours. There is no evidence of accumulation or enzyme induction (Cytochrome P450) following multiple oral doses.
Excretion is almost totally urinary; the main biotransformation product is Metabolite V. Essentially no parent drug is found in the urine. Despite large variations in plasma levels of parent compound and its metabolites, the urinary recovery of Metabolite V is consistent and shows dose proportionality. Less than 4% of the administered dose is recovered in feces. Food intake shortly before dosing delays absorption of an immediate-release dosage form but does not affect total absorption. The pharmacokinetics and metabolism of TRENTAL have not been studied in patients with renal and/or hepatic dysfunction. The pentoxifylline AUC was increased and elimination rate decreased in an older population (60–68 years, n=6) compared to younger individuals (22–30 years, n=6) (see PRECAUTIONS, Geriatric Use).
After administration of the 400 mg extended-release TRENTAL tablet, plasma levels of the parent compound and its metabolites reach their maximum within 2 to 4 hours and remain constant over an extended period of time. Coadministration of TRENTAL tablets with meals resulted in an increase in mean Cmax and AUC by about 28% and 13% for pentoxifylline, respectively. Cmax for Metabolite 1 also increased by about 20%. The extended release of pentoxifylline from the tablet eliminates peaks and troughs in plasma levels for improved gastrointestinal tolerance.
INDICATIONS AND USAGE
TRENTAL is indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. TRENTAL can improve function and symptoms but is not intended to replace more definitive therapy, such as surgical bypass, or removal of arterial obstructions when treating peripheral vascular disease.
CONTRAINDICATIONS
TRENTAL should not be used in patients with recent cerebral and/or retinal hemorrhage or in patients who have previously exhibited intolerance to this product or methylxanthines such as caffeine, theophylline, and theobromine.
PRECAUTIONS
General
Patients with chronic occlusive arterial disease of the limbs frequently show other manifestations of arteriosclerotic disease. TRENTAL has been used safely for treatment of peripheral arterial disease in patients with concurrent coronary artery and cerebrovascular diseases, but there have been occasional reports of angina, hypotension, and arrhythmia. Controlled trials do not show that TRENTAL causes such adverse effects more often than placebo, but, as it is a methylxanthine derivative, it is possible some individuals will experience such responses. Patients on Warfarin should have more frequent monitoring of prothrombin times, while patients with other risk factors complicated by hemorrhage (e.g., recent surgery, peptic ulceration, cerebral and/or retinal bleeding) should have periodic examinations for bleeding including, hematocrit and/or hemoglobin.
Drug Interactions
Although a causal relationship has not been established, there have been reports of bleeding and/or prolonged prothrombin time in patients treated with TRENTAL with and without anticoagulants or platelet aggregation inhibitors. Patients on Warfarin should have more frequent monitoring of prothrombin times, while patients with other risk factors complicated by hemorrhage (e.g., recent surgery, peptic ulceration) should have periodic examinations for bleeding including hematocrit and/or hemoglobin. Concomitant administration of TRENTAL and theophylline-containing drugs leads to increased theophylline levels and theophylline toxicity in some individuals. Such patients should be closely monitored for signs of toxicity and have their theophylline dosage adjusted as necessary. TRENTAL has been used concurrently with antihypertensive drugs, beta blockers, digitalis, diuretics, antidiabetic agents, and antiarrhythmics, without observed problems. Small decreases in blood pressure have been observed in some patients treated with TRENTAL; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensive therapy. If indicated, dosage of the antihypertensive agents should be reduced.
Carcinogenesis, Mutagenesis and Impairment of Fertility
Long-term studies of the carcinogenic potential of pentoxifylline were conducted in mice and rats by dietary administration of the drug at doses up to 450 mg/kg (approximately 19 times the maximum recommended human daily dose (MRHD) in both species when based on body weight; 1.5 times the MRHD in the mouse and 3.3 times the MRHD in the rat when based on body surface area). In mice, the drug was administered for 18 months, whereas in rats, the drug was administered for 18 months followed by an additional 6 months without drug exposure. In the rat study, there was a statistically significant increase in benign mammary fibroadenomas in females of the 450 mg/kg group. The relevance of this finding to human use is uncertain. Pentoxifylline was devoid of mutagenic activity in various strains of Salmonella (Ames test) and in cultured mammalian cells (unscheduled DNA synthesis test) when tested in the presence and absence of metabolic activation. It was also negative in the in vivo mouse micronucleus test.
Pregnancy
Category C. Teratogenicity studies have been performed in rats and rabbits using oral doses up to 576 and 264 mg/kg, respectively. On a weight basis, these doses are 24 and 11 times the maximum recommended human daily dose (MRHD); on a body-surface-area basis, they are 4.2 and 3.5 times the MRHD. No evidence of fetal malformation was observed. Increased resorption was seen in rats of the 576 mg/kg group. There are no adequate and well controlled studies in pregnant women. TRENTAL (pentoxifylline) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
Pentoxifylline and its metabolites are excreted in human milk. Because of the potential for tumorigenicity shown for pentoxifylline in rats, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Clinical studies of TRENTAL did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
The active metabolite is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
ADVERSE REACTIONS
Clinical trials were conducted using either extended-release TRENTAL tablets for up to 60 weeks or immediate-release TRENTAL capsules for up to 24 weeks. Dosage ranges in the tablet studies were 400 mg bid to tid and in the capsule studies, 200–400 mg tid. The table summarizes the incidence (in percent) of adverse reactions considered drug related, as well as the numbers of patients who received extended-release TRENTAL tablets, immediate-release TRENTAL capsules, or the corresponding placebos. The incidence of adverse reactions was higher in the capsule studies (where dose related increases were seen in digestive and nervous system side effects) than in the tablet studies. Studies with the capsule include domestic experience, whereas studies with the extended-release tablets were conducted outside the U.S.
The table indicates that in the tablet studies few patients discontinued because of adverse effects.

INCIDENCE (%) OF SIDE EFFECTS

	Extended-Release Tablets		Immediate-Release Capsules
	Commercially Available		Used only for Controlled Clinical Trials
	TRENTAL	Placebo	TRENTAL	Placebo
(Numbers of Patients at Risk)	(321)	(128)	(177)	(138)
Discontinued for Side Effect	3.1	0	9.6	7.2
CARDIOVASCULAR SYSTEM
Angina/Chest Pain	0.3	-	1.1	2.2
Arrhythmia/Palpitation	-	-	1.7	0.7
Flushing	-	-	2.3	0.7
DIGESTIVE SYSTEM
Abdominal Discomfort	-	-	4.0	1.4
Belching/Flatus/Bloating	0.6	-	9.0	3.6
Diarrhea	-	-	3.4	2.9
Dyspepsia	2.8	4.7	9.6	2.9
Nausea	2.2	0.8	28.8	8.7
Vomiting	1.2	-	4.5	0.7
NERVOUS SYSTEM
Agitation/Nervousness	-	-	1.7	0.7
Dizziness	1.9	3.1	11.9	4.3
Drowsiness	-	-	1.1	5.8
Headache	1.2	1.6	6.2	5.8
Insomnia	-	-	2.3	2.2
Tremor	0.3	0.8	-	-
Blurred Vision	-	-	2.3	1.4

TRENTAL has been marketed in Europe and elsewhere since 1972. In addition to the above symptoms, the following have been reported spontaneously since marketing or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain:
Cardiovascular - dyspnea, edema, hypotension. 
Digestive - anorexia, cholecystitis, constipation, dry mouth/thirst.
Nervous - anxiety, confusion, depression, seizures, aseptic meningitis. 
Respiratory - epistaxis, flu-like symptoms, laryngitis, nasal congestion. 
Skin and Appendages - brittle fingernails, pruritus, rash, urticaria, angioedema.
Special Senses - blurred vision, conjunctivitis, earache, scotoma.
Miscellaneous - bad taste, excessive salivation, leukopenia, malaise, sore throat/swollen neck glands, weight change.
A few rare events have been reported spontaneously worldwide since marketing in 1972. Although they occurred under circumstances in which a causal relationship with pentoxifylline could not be established, they are listed to serve as information for physicians. Cardiovascular — angina, arrhythmia, tachycardia, anaphylactoid reactions. Digestive — hepatitis, jaundice, increased liver enzymes; and Hemic and Lymphatic — decreased serum fibrinogen, pancytopenia, aplastic anemia, leukemia, purpura, thrombocytopenia.
OVERDOSAGE
Overdosage with TRENTAL has been reported in pediatric patients and adults. Symptoms appear to be dose related. A report from a poison control center on 44 patients taking overdoses of enteric-coated pentoxifylline tablets noted that symptoms usually occurred 4–5 hours after ingestion and lasted about 12 hours. The highest amount ingested was 80 mg/kg; flushing, hypotension, convulsions, somnolence, loss of consciousness, fever, and agitation occurred. All patients recovered. In addition to symptomatic treatment and gastric lavage, special attention must be given to supporting respiration, maintaining systemic blood pressure, and controlling convulsions. Activated charcoal has been used to absorb pentoxifylline in patients who have overdosed.
DOSAGE AND ADMINISTRATION
The usual dosage of TRENTAL in extended-release tablet form is one tablet (400 mg) three times a day with meals.
While the effect of TRENTAL may be seen within 2 to 4 weeks, it is recommended that treatment be continued for at least 8 weeks. Efficacy has been demonstrated in double-blind clinical studies of 6 months duration.
Digestive and central nervous system side effects are dose related. If patients develop these effects it is recommended that the dosage be lowered to one tablet twice a day (800 mg/day). If side effects persist at this lower dosage, the administration of TRENTAL should be discontinued.
HOW SUPPLIED
TRENTAL (pentoxifylline) is available for oral administration as 400-mg pink film-coated oblong tablets imprinted Trental; supplied in bottles of 100 (NDC 0039-0078-10).
Store between 59 and 86° F (15 and 30° C).
http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=9211