A PHARMACOKINETIC STUDY

OF

AEKNIL (PARACETAMOL) INJECTION

OBJECTIVE 

To determine the pharmacokinetic behavior of an intra-muscular injection of a preparation of Paracetamol (AEKNIL) in normal healthy adults. 

MATERIAL 

Test formulation (AEKNIL) containing 150 mg/ml of Paracetamol. 

METHODS 

A.     Subject 

Seven healthy volunteers of either sex ranging in age from 21 to 50 years, weighing not less than 80lbs and not more than 150lbs who gave their informed consent participated in this single-dose study. 

Prior to the study, a history and physical examination as well as laboratory tests (complete blood count, urinalysis, fasting blood sugar, blood urea nitrogen, serum creatinine, total serum protein, serum albumin, serum globulin, SGDT & alkaline phosphatase) were conducted on every subject to confirm that they were free from any identifiable medical disorder. None of the subjects were on any drugs during the experiment and for at least two weeks prior to the experiment.

EXPERIMENTAL PROCEDURE 

The experiment was performed with subjects in a fasting state (overnight and for 2 hours after dosing). Subjects were not allowed to smoke but water was permitted ad libitum. They were free to ambulate during the study but were not allowed strenuous activity. 

An indwelling catheter (Abbocath) was inserted into an antecubital vein. A baseline blood sample was taken after which the subject was injected intramuscularly with 2ml of the test drug containing 150mg/ml of Paracetamol. Thereafter, serial blood extractions at 15min 30min, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours were done. Regular meals were provided after the 2^nd blood extraction. 

Sera were separated from each blood sample by centrifugation. Proper coding and labeling and other precautionary measures were strictly observed. Sera were frozen at –20° C until the acetaminophen assay were performed.
 

PARACETAMOL ASSAY 

Paracetamol analyses were carried out within three weeks after blood extraction using the Spectrophotometric method of Brodie and Axlerod. The lower limit of sensitivity methods is 0.2mg Paracetamol per milliliter of sample. 

Paracetamol was extracted with ether from the biological sample. The reaction was hastened by saturating the aqueous phase with Sodium Chloride. The mixture was then made alkaline and hydrolyzed in acid to p-Aminophenol. The p-Aminophenol was diazotized and coupled with alpha-naphtal to form a dye, which was then assayed spectrophotometrically at 510 mu on a Beckman DU-6 Spectrophotometer. 

Throughout the analysis, reagent blanks were used for zero setting of the instrument. Likewise, to correct for any variations in absorbance, standards were simultaneously run.  The mean readings between trial runs were noted.

PARAMETERS OF PHARMACOKINETIC BEHAVIOUR 

The parameters of pharmacokinetic behavior considered are: 

1.   The peak height concentration (C max) 

2.   The time to peak concentration (T max) 

3.   The area under the serum concentration – time (AUC)
 

RESULTS 

1.   Table 1 lists the individual Paracetamol concentrations of the seven subjects observed at different times following using with the test formulation. 

2.   Table 3 lists the C max, T max and AUC of the test formulation.