Phenacetin drug

Similar methods with modifications such as the one by Schutz et al.8 have been in use for over 20 years. In 1968, Ferren and Shane9 published a paper on the differential spectrometric determination of caffeine in soluble coffee and drug combinations. It had the advantage of eliminating a preliminary separation that was required by the earlier method. While the method was successful for coffee, it was not as successful in the determination of caffeine in acetaminophen/phenacetin/caffeine tablets. They proposed that phenacetin was a limiting factor. The official AOAC methods for these methylxanthines in coffee and tea still involve similar methods.10... 

Fig. 11 Effect of particle size of phenacetin on dissolution of drug from granules containing starch and gelatin. Q, particle size 0.11-0.15mm A, particle size 0.15-0.21 mm , particle size 0.21-0.30mm , particle size 0.30-0.50mm , particle size 0.50-0.71 mm. (From Ref. 17.).

In addition to these in vitro demonstrations of the importance of the effective surface area of drug particles on dissolution rate, many in vivo studies are available. Phenacetin plasma levels versus time are plotted for three different particle sizes of phenacetin in Fig. 14. Healthy adult volunteers received 1.5-g doses of phenacetin as an aqueous suspension on an empty stomach. The results show that both the rate and... 

Lot to lot variations of several drugs and excipients are shown in Table 9. Specially crystallized lots of ibuprofen, for example, show substantial changes in Brittle Fracture and Bonding Indices. Phenacetin shows a significant increase in brittleness at higher relative humidity. It was observed by Hiestand and Smith [31] that compacts of dried phenacetin did not fracture, while the lot equilibrated at 40% relative humidity did, consistent with the Brittle Fracture Index change. 

Rodrigues, A.D. et al. 1997. [O-ethyl 14C]phenacetin O-deethylase activity in human liver micro-somes. Drug Metab. Dispos. 25 1097. 

Procedure The drug contents of an appropriate number of tablets are directly extracted into chloroform, filtered if necessary so as to remove the insoluble tablet components, and the final concentration of chloroform solution is made in such a way so that it should contain 90 mg ml-1 of aspirin 64 mg ml 1 of phenacetin, and 134 mg ml-1 of caffeine. The IR-spectrum is now recorded in a 0.1 mm NaCl-cell between 1400-2000 cm-1. 

G. S. Estus, J. J. Mieyal, Structure-Activity Relationship for Deacetylation of a Homologous Series of Phenacetin Analogs and Their V-Hydroxy Derivatives , Drug Metab. Dispos. 1983, 11, 471-476. 

The performance of the activated sludge process for the treatment of wastewater from a synthetic drug factory, has been reported [14,15,45]. One of the biggest plants of its kind in Asia, M/S Indian Drugs and Pharmaceutical Ltd., Hyderabad, went into production in 1966 to make sulfa drugs such as sulfanilamides antipyretics (phenacetin), B-group vitamins, antimbercular drugs (isonicotinic acid hydrazide) and antihelminthics, and so on. 

Generally, the liver is the center of drug metabolism, hence numerous drugs and methods to measure functional hepatic capacity are available. A host of these methods rely on the metabolic activity of cytochrome P450 enzymes, and some of the markers used include phenacetin, methacetin, trimethadione. 

During the year there were a number of reports in the press of deaths associated with phen-acetin. The Committee emphasised that the hazard was associated with the abuse of the drug (excessive doses taken over a long term) and reiterated that, consequently, no special action was necessary. Furthermore, because a drug (including phenacetin) could be marketed under different proprietary names, it could confuse a doctor. Therefore, the Committee decided that they would not consider an application by a manufacturer to market a new substance unless the applicant gave an assurance that an approved name had been obtained or applied for. 

During 1969-70, the nephropathic hazards of phenacetin again attracted much attention and the Committee made a seminal observation that has profoundly influenced our regulatory philosophy even today It is the safety of drugs in normal usage that is the Committee s concern, and because all drugs have their hazards when abused, particularly by over-dosage, the Committee has not considered that it should take special action in connection with phenacetin. ... 

Acetaminophen is one of the most important drugs used in the treatment of mild to moderate pain when an anti-inflammatory effect is not necessary. Phenacetin, a prodrug that is metabolized to acetaminophen, is more toxic than its active metabolite and has no rational indications. 

Despite the resolving power of TLC-MS-MS, few applications in drug residue analysis have been reported. One application concerns the HPTLC-MS-MS analysis of a number of nonsteroidal anti-inflammatory drugs, including salicylic acid and its glycine conjugate salicylhippuric acid, diclofenac, indomethacin, naproxen, phenacetin, and ibuprofen (67). Another application describes the detection and identification of some of these compounds or their metabolites in urine by TLC-MS-MS (67). 

The hydrolysis of some amides may be catalyzed by a liver microsomal carboxyl esterase, as is the case with phenacetin (Fig. 4.44). Hydrolysis of the acetylamino group, resulting in deacetylation, is known to be important in the toxicity of a number of compounds. For example, the deacetylated metabolites of phenacetin are thought to be responsible for its toxicity, the oxidation of hemoglobin to methemoglobin. This toxic effect occasionally occurs in subjects taking therapeutic doses of the drug and who have a deficiency in the normal pathway of metabolism of phenacetin to paracetamol. Consequently, more phenacetin is metabolized by deacetylation and subsequent oxidation to toxic metabolites (chap. 5, Fig. 24). 

The defective de-ethylation of phenacetin was discovered in a patient suffering methemoglobinemia after a reasonably small dose of the drug. This toxic effect was observed in a sister of the patient but not in other members of the family. The metabolism of phenacetin in the patient and in the sister was found to involve the production of large amounts of the normally minor metabolites 2-hydroxy phenacetin and 2-hydroxyphenetidine, with a concomitant reduction in the excretion of paracetamol, the major metabolic product of... 

Amidation of alkyl aryl ethers.2 Either anisole or phenetole undergoes para-amidation exclusively on reaction with acetohydroxamic acid in polyphosphoric acid (yields 50-60%). Thus phenetole is converted into the drug phenacetin in -50% yield (equation I). 

ANTIPYRETIC. Any physical agent or drug that lowers the temperature of the body. Among antipyretics used are aspirin, antipyrine. acetanilid, and phenacetin. See also Analgesics, Antipyretics, and Antiinflammatory Agents. 

Figure 11.5 Chromatograms of plasma samples obtained with fully automated on-line SPE-LC (a) drug-free human plasma (b) human plasma spiked with omeprazole (100 ng/ml) and phenacetin (internal standard 1000 ng/ml). Reprinted from Journal of Pharmaceutical and Biomedical Analysis, 21, G. Garcia-Encina et al., Validation of an automated liquid chromatographic method for omeprazole in human plasma using on-line solid-phase extraction, pp. 371-382, copyright 1999, with permission from Elsevier Science.

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