Primidone

Sample material Serum or plasma. Serum and plasma samples can be stored in the refrigerator for one week at +2°C to +8°C. 

Specificity The substances tabulated below produce a 25% increase if they are added in a concentration of 1250 mg/1 to a sample containing 5 mg/1 primi-  

Drug or metabolite in sample Concentration usually appearing in serum [mg/1] 

Imprecision (in the clinically relevant range).- 10%. Accuracy Correlation coefficient = 0.981-0.990. Interferences See Amikacin. 

Aktiebolaget Astra Apotekarnes Kemiska Fabriker, Sweden British Patent 839,943 June 29, 1960 

Chemical Name 5-Ethvldihvdro-5-phenyl-4,6(1 H,5H)-pyrimidinedione Common Name 2-Oesoxyphenobarbital primaclone 

Trade Name Manufacturer Country Year Introduced 

50 parts of a,o-phenylethylmalondiamide and 150 parts of formamide are boiled together under reflux for 2 hours. The mixture is then cooled to 0°C and filtered. The solid residue is washed with 50 parts of ethanol and then crystallized from 660 parts of an 80% ethanol water mixture. There is obtained 5-phenyl-5-ethylhexahydropyrimidine-4,6-dione, MP 281°-282°C. 

Carrington, H.C. and Vasey, C.H. U.S. Patent 2,576,647 December 16, 1951 assigned to Imperial Chemical Industries Limited, England 

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Primidone [125-33-7] C22H24N2O2 (39) is an analogue of phenobarbital that is used for the treatment of generalized tonic-clonic seizures. It is metabolized in humans to phenobarbital (6) and phenylethyLmalondiamide [7206-76-0J, C22H24N2O2 (40) and these metaboUtes are probably responsible for its anticonvulsant actions. Primidone has many of the side effect HabiUties seen with phenobarbital. 

These have generally been replaced in veterinary medicine by inhalation anesthetics. Phenobarbital /T(9-(9G, phenytan [57-41-0], and primidone [125-33-7] are used as anticonvulsants. 

The anticonvulsant primidone (1035) resembles phenobarbital but lacks the 2-oxo substituent. It was introduced in 1952 and has remained a valuable drug for controlling grand mal and psychomotor epilepsy. As might be expected, primidone is metabolized to yield phenobarbital (1034 X = 0) and C-ethyl-C-phenylmalondiamide (1036), both of which have marked anticonvulsant properties however, primidone does have intrinsic activity and an appropriate mixture of its metabolites has only a fraction of its activity (73MI21303). Primidone may be made in several ways, of which desulfurization by Raney nickel of the 2-thiobarbiturate (1034 X = S) or treatment of the diamide (1036) with formic acid (at 190 °C) seem to be the most satisfactory (54JCS3263). 

Detection and result The chromatogram was freed from mobile phase (first dried for 5 min in a stream of cold air, then heated for 10 min at 110°C and allowed to cool), immersed for 5 s in the reagent solution and finally heated for 2 min at 110°C. Grey to grey-blue zones were formed on a light background. The following hRf values were obtained primidone QiR( 10-15) carbamazepine hRf 40 — 45) phenytoin hR( 50 — 55) phenobarbital hRf 60) ethosuximide hRf 75) hexobarbital hRf 90 — 95). 

Fig. 1 Reflectance scan of a blank (A) and of a mixture of antiepileptics with 500 ng substance per chromatogram zone (B). Start (1), primidone (2), carbamazepine (3), phenytoin (4), phenobarbital (5), ethosuximide (6), hexobarbital (7) and solvent front (8).

Prilocaine 1, 17 Primaquine 1, 346 Primidolol 29 Primidone j, 276 Prizidilol 151 Probarbital 268... 

Fluoro uracil mercury Tegafur Formaldehyde Biperiden Bronopol Cortivazol Edetate disodium Glaziovine Hexetidine Meptazinol Metampicillin sodium Methylol riboflavin Nifurfoline Nifurtoinol Noxytiolin Oxymetazoline HCI Phenindamine tartrate Pipebuzone Thihexinol Timonacic sodium Triclobisonium chloride T romethamine Tyloxapol Formamide Cimetide Primidone Protriptyline Razo xane Spiperone Formic acid Bupivacaine... 

When the hydantoins are administered with the suc-cinimides there may be an increase in the hydantoin blood levels. Concurrent administration of valproic acid and the succinimides may result in either a decrease or an increase in succinimide blood levels. When primidone in administered with the succinimides, lower primidone levels may occur. 

When carbamazepine is administered with primidone, decreased primidone levels and higher carbamazepine serum levels may result. Cimetidine administered with carbamazepine may result in an increase in plasma levels of carbamazepine that can lead to toxicity. Blood levels of lamotrigine increase when the agent is administered with valproic acid, requiring a lower dosage of lamotrigine... 

There is an increased risk of cyclosporine toxicity when the drug is administered with acetazolamide. Decreased serum and urine concentrations of primidone occur when the drug is administered with acetazolamide. 

QH12N2 19275-55-9) see Etodolac ethylphenylmalondiamide (C11H14N2O2 7206-76-0) see Primidone ethylphenylmalonic acid diethyl ester see under diethyl cthylphenylmalonate... 

CH3NO 75-12-7) see Allopurinol Chlorothiazide Cimetidine Fludarabinc phosphate Fluspirilene Heptaminol Primidone Protriptyline Pyridoxine Razoxane Sulfadoxine Theophylline... 

Primidone GM/PE Works partly by conversion to phenobarbitone in body... 

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