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| Year : 1985 | Volume
: 31
| Issue : 4 | Page : 192-5 |
Bioavailability of aspirin after oral and rectal administration in volunteers and patients with fever.
Dalvi SS, Gupta KC, Pohujani SM, Vaidya AB, Satoskar RS
How to cite this article:
Dalvi S S, Gupta K C, Pohujani S M, Vaidya A B, Satoskar R S. Bioavailability of aspirin after oral and rectal administration in volunteers and patients with fever. J Postgrad Med 1985;31:192 |
How to cite this URL:
Dalvi S S, Gupta K C, Pohujani S M, Vaidya A B, Satoskar R S. Bioavailability of aspirin after oral and rectal administration in volunteers and patients with fever. J Postgrad Med [serial online] 1985 [cited 2023 Sep 26];31:192. Available from: https://www.jpgmonline.com/text.asp?1985/31/4/192/5384 |
Medication in the form of suppositories for local and systemic effect offers some advantages in certain clinical situations. Aspirin is often used in capsules given rectally for relief of pain or fever. For this purpose, aspirin in a gelatin capsule is punctured with a pin, dipped in water and inserted. This route is sometimes preferred in patients with high fever in whom oral aspirin is either difficult to administer or is contraindicated due to vomiting. This study describes the bioavailability of aspirin after rectal administration as compared to the same dose given orally, in volunteers and in patients with fever.
(A) Volunteer Study: The study was carried out in 5 healthy male volunteers, with an age range between 22 and 44 years. They were examined clinically and routine biochemical and hematological tests were carried out. Informed consent was obtained. Each volunteer received two preparations: a single dose of 2 tablets of 300 mg aspirin orally and 2 suppositories each containing 300 mg of aspirin in a randomized fashion with a washout period of 7 days in between the two administration. After bowel evacuation in the morning, suppositories were inserted rectally by the house officer.
Blood was collected in heparinized tubes at 0, 15, 30, 45 minutes and 1, 2, 4, 6 and 8 hours. Plasma was immediately separated and stored at -4°C, till analysed. Light breakfast was given 1 hour after oral administration of aspirin. Volunteers who received suppositories were kept in supine position for 2 hours. Each volunteer was asked about expulsion of the suppository and any irritation in the anorectal region. Molded suppositories were prepared in 2 types of bases viz. cocoa, butter and suppositrin (variety of witepsol base) by fusion process.[2]
(B) Studies in patients with fever: Seven patients with fever due to upper respiratory tract infections with temperature ranging from 101°F to 104°F and without other complications were taken up for this study.
Patients remained recumbent till the study was completed. No other antipyretic was used during the 4 hour period. Study in fever patients was carried out with rectal administration of 2 suppositories in suppositrin base (300 mg each). At the end of the study, irritation or burning sensation in the anorectal region and expulsion of suppository was not reported by any of these patients.
Blood samples were collected at 0, 1, 2, 3 and 4 hours. Blood pressure, pulse and temperature were recorded at half-hour intervals.
Plasma salicylate levels were estimated spectrophotometrically by Trinder's method.[10]Recovery by this method was 98-100%. The area under plasma concentration versus time (AUC) was determined by trapezoidal rule in volunteers.
Volunteer Study:[Fig. 1], shows the results of plasma salicylate levels after oral and rectal administration of 600 mg aspirin. After oral administration, plasma salicylate levels were detectable at 15 minutes. T max was at 2 hours followed by a gradual fall upto 8 hours. As compared to this, with cocoa butter suppositories, salicylate levels were not detectable in plasma. With the use of suppositrin suppositories, detectable plasma salicylate levels were obtained at 45 minutes and T max at 4 hours. The AUC for oral aspirin was significantly higher than that of suppository in suppositrin base (p < 0.001).
Patient Study: In patients with fever, plasma salicylate levels with aspirin suppositories were higher as compared to those in volunteers. Detectable levels of salicylates were observed at 1 hour. C max was obtained in 3 hours[Fig. 1]. Antipyretic effect was observed at 1 hour in 1 patient, between 2-2V2 hours in 3 patients and at 3 hours in 2 patients. In 1 patient, maximum fall in temperature occurred at 4 hours. Frequent blood collection was not possible in patients with fever, hence blood collections were done only upto 4 hours and AUC was not calculated.
After oral administration of 600 mg aspirin, the maximum mean plasma salicylate concentration C max was 40.5 mg/L at 2 hours. Considering this value as 100 %, C max for suppositories (suppositrin base) in volunteers was 22,6 mg/L (55.8%) at 4 hours. In fever patients, C RAUI was 30 mg/L (74%) and T max was 3 hours.
Rectum represents a body cavity in which drugs can be easily introduced and retained. It has been preferred especially in cases where nausea or vomiting is present and in elderly people.
Boer et al[3]have studied the clinical pharmacokinetic aspects of rectal drug administration and the role of physiological factors in rectal absorption of drugs. Thus, pH and fluid content of the rectum may influence the dissolution of the drug.[1],[6]Smaller surface of the rectum as compared to the upper G.I. tract may give rise to less absorption.
In the first part of the study, there was delayed absorption of salicylate after rectal administration as compared to oral administration. This may be because of physiological factors mentioned earlier as well as the nature of suppository base. Cacchilo and Hasler[4]and Parrot[8]reported that water soluble sodium salicylate is more readily released from the suppository base than water insoluble aspirin. Plasma salicylate levels reached after oral administration were comparable with those reported by of Cacchilo and Hasler[4]and Samelius.[9]Earlier studies on rectal absorption of aspirin indicated that rectal absorption is slower as compared to orally administered aspirin. Coldwell et al[5]and Gibaldi and Grandhofer[7] showed that rectal absorption in various commercially available preparations varied from 20%-40%. Cacchilo and Hasler[4]demonstrated that absorption of aspirin from cocoa butter base was 65.5% and from carbowax base 94.1%, oral absorption levels being taken as 100%; they concluded that suppositories of water soluble bases give levels equivalent to oral administration. However, in the present study, absorption from cocoa butter suppositories was negligible upto 6 hours and from suppositrin base, it was 55.8% in volunteers and 74% in febrile patients.
The absorption of aspirin from suppositrin base in fever patients was more as compared to volunteers and C max reached earlier. This may be attributed to the hyperaemia and submucosal vasodilation.
| 1. | Bechgaard, E. I.: Absorption of salicylic acid from the perfused human rectum. Acta Pharmacol. et Toxicol., 33: 129-137, 1973.  |
| 2. | Blaug, S. M.: Medicated applications. In "Remington's Pharmaceutical Science," XVth edution. Maac Publishing Company, 1523-1553, 1975. |
| 3. | Boer, A. G., Moolenaar, F., de Leeds, L. G. J. and Breimer, D. D.: Rectal drug administration: Clinical pharmacokinetic considerations. Clin. Pharmacokin., 7: 285-311, 1982. |
| 4. | Cacchilo, A. F. and Hasler. W. H.: The influence of suppository bases upon rectal absorption of acetylsalicylic acid. J. Amer. Pharmaceu. Assoc., 43: 685, 1954. |
| 5. | Coldwell, B. B., Solomonray, G., Boyd. F. M., Jantz, J. and Morrison, A. B.: The effect of dosage form and route of administration on the absorption and excretion. of acetylsalicylic acid in man Clin. Toxicol., 2: 111-127, 1969. |
| 6. | Crouthamel, W. G.,. Tan, G. H., Differt, L. W. and Daluisio, J. T.: Drug absorption; Influence of pH on absorption kinetics of weak acidic drugs. J. Pharmaceu. Sci., 60: 1160-1163, 1971. |
| 7. | Gibaldi, M. and Grandhofer, B.: Bioavailability of aspirin from commercial suppositories. J. Pharmaceu. Sci., 64: 1064 1066, 1975. |
| 8. | Parrot, E. L.: Salicylate absorption from rectal suppositories. J. Pharmaceu. Sci., 60: 867-892, 1971. |
| 9. | Samelium, U. and Astrom, A.: The absorption of N-methylated barbiturates and acetyl salicylic acid from different suppository massess. Acta Pharmacol. et Toxicol., 14: 240-250, 1958. |
| 10. | Trinder, P.: Rapid determination of salicylates in biological fluids. Biochem. J., 57: 301-308, 1954. |
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