Br. J. clin. Pharmac.

(1986), 22, 111-113

Paracetamol absorption from a feeding jejunostomy

E. B. NELSON1, D. R. ABERNETHY1, D. J. GREENBLATr2 & BARBARA AMEER3 'Section on Hypertension and Clinical Pharmacology, Department of Medicine, Baylor College of Medicine, Houston, Texas, 2Division of Clinical Pharmacology, Departments of Psychiatry and Medicine, Tufts University School of Medicine and New England Medical Center Hospital, Boston, Massachusetts and 3University of Florida College of Pharmacy, Gainesville, Florida, USA

Disposition of paracetamol oral elixir was determined in two male patients after administration via feeding jejunostomy and compared with four male controls who received the same dose by mouth. Area under the plasma concentration-time curve, elimination halflife, and time to maximum concentration were similar in both groups after 650 mg paracetamol elixir. The absolute amounts and ratio of paracetamol glucuronide to sulphate, the major urinary metabolites after therapeutic paracetamol doses, were similar after jejunal administration as compared to oral administration. Paracetamol is absorbed and biotransformed in a similar manner after either jejunal or oral administration. Therefore, it may be administered effectively via jejunostomy tube in patients who require this route of administration.
Keywords paracetamol absorption jejunostomy
Introduction

The absorption of drugs after jejunal admin- via the jejunum or after oral administration. istration via a feeding jejunostomy has not been Therefore, a similar dosing regimen for paraextensively evaluated. Previously, Nelson & cetamol when administered either by mouth or Levitt (1980) demonstrated that aspirin was well via jejunostomy tube is appropriate. absorbed from a jejunostomy. Metabolic products were not analyzed. Magnusson (1983) demonstrated alteration of digoxin metabolism when Methods comparing oral to jejunal instillation. Frequently, patients with malignancy or neurological dis- After giving written informed consent, four orders have a jejunostomy tube placed as a normal male volunteers were recruited as part of means of nutritional support. Commonly used a study evaluating paracetamol kinetics. Two drugs might be administered via this route if male patients were hospitalized, both with a disposition is not affected when given via the malignancy which required gastrectomy. Each jejunum. Recently, we cared for two patients had a feeding jejunostomy tube placed at the with jejunostomy tubes in place for nutritional time of surgery in order to facilitate postoperative support and in whom paracetamol therapy was feeding. In both patients, the use of paracetamol appropriate. To ascertain the effectiveness of as an analgesic was indicated. Patient 2 had jejunal administration, we compared para- biopsy evidence of hepatic metastases; neither cetamol disposition in these two patients to four was receiving chemotherapy, and both had elderly males who received the same dose (650 normal creatinine and bilirubin levels. Patient 1 mg) of paracetamol elixir by mouth. These results was receiving radiotherapy to the neck. Patient 2 indicate that paracetamol is comparably absorbed was not receiving any therapy other than alimenCorrespondence: Dr E. B. Nelson, Section on Hypertension and Clinical Pharmacology, 6535 Fannin, Mail Station F504, Houston, Texas, USA 77030

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pared with the four control subjects who received paracetamol by mouth in Table 1. This is shown graphically in Figure 1 which shows the plasma concentration curve vs time for a control subject compared with patient 1. The elimination halflives (approximately 2.5 to 3 h) and peak concentrations were similar. Total area under the curve was greater in the two jejunostomy patients compared to the control subjects. Neither of the patients noted any discomfort from the administration of paracetamol by instillation into their jejunostomy tube. To assess the effect of route of administration on urinary metabolite profile, urinary paracetamol metabolites were measured in the

tation. Both were studied at least 2 weeks postoperatively. Paracetamol 650 mg as the commercial elixir (Tylenol elixir, McNeil, Fort Washington, Pennsylvania, USA) was given by mouth to the elderly volunteers after an overnight fast. In the two patients with a jejunostomy tube, the same dose of 650 mg of paracetamol elixir was mixed with 80 ml of the alimentation solution (Vivonex, Norwich Eaton, Norwich, New York, USA) and water 1:1 mixture. The tube was then flushed with 50-75 ml of Vivonex:water mixture and then clamped for 30 min. Multiple plasma samples were obtained over the following 24 h as shown in Figure 1. A 24 h urine collection was also obtained and analyzed for paracetamol and the glucuronide and sulphate metabolites. Plasma paracetamol was measured by high pressure liquid chromatography (Ameer et al., 1981), and paracetamol sulphate and glucuronide were measured directly in the urine in a similar manner (Ameer et al., 1984). Area under the plasma concentration-time curve (AUC) was determined by the trapezoidal method and extrapolated to infinity by dividing the terminal point by the 3-slope. The elimination half-life was determined from the slope of the log linear elimination curve, and peak plasma concentration was established by direct observation. Results
The kinetics of disposition of paracetamol in the two patients after jejunal administration is comTable 1 Paracetamol kinetics

,If%

E 10
0

o1

E
1.0
(I)

1-c

Time after dose (h) Figure 1 Plasma concentrations of paracetamol in a volunteer who took 650 mg elixir orally (O) and in a patient who took paracetamol 650 mg via a feeding jejunostomy (A).

Hospitalized patients
1 2 1

Normal volunteers
2 74 74 3
74 4

Age (years)

51
65

Weight (kg)
Plasma kinetics Elimination half-life (h) Peak concentration (p,g m17') Total AUC (tLg m17' h)

72 88 3.0 12.1 35.5 32 302

68 77

90
2.5

70 88

2.8 12.5 39.3 20 204

190

2.6 14.1 29.7

2.8 10.1 29.5

5.1
26.8

2.4 12.5 17.9

Urinary excretion Paracetamol (mg 24 h-1) Paracetamol glucuronide* (mg 24 h1) Paracetamol sulphate* (mg 24 h-1)

183

*Expressed as mg paracetamol equivalent

Short report
jejunostomy patients. Approximately 80% of the dose was accounted for by the glucuronide and sulphate metabolites. This is similar to that noted after oral administration (Abernethy et al., 1985). The ratio of glucuronide to sulphate is similar to that seen in previous studies (Abernethy et al., 1985).
Discussion Peak paracetamol concentration and time to peak concentration were similar in the control patients and the two jejunostomy patients. This suggests that the rate of paracetamol absorption is similar after either oral or jejunal administration. In this small group of patients, no definitive statement with regards to the increased area under the curve can be made. Paracetamol given via the jejunum was predominantly biotransformed to the glucuronide
References
Abernethy, D. R., Greenblatt, D. J., Ameer, B. & Shader, R. I. (1985). Probenecid impairment of acetominophen and lorazepam clearance: direct inhibition of ether glucuronide formation. J. Pharmac. exp. Ther., 234, 345-349. Ameer, B., Abernethy, D. R. & Greenblatt, D. J. (1984). Direct quantitation of glucuronide and sulfate metabolites of acetaminophen in urine. J. clin. Pharmac., 24, 393-394. Ameer, B., Greenblatt, D. J., Divoll, M. M., Abernethy, D. R. & Shargel, L. (1981). High pressure liquid chromatographic determination of acetaminophen in plasma: single dose pharmacokinetic studies. J. Chromatogr., 226, 224-230.

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and sulphate conjugates in a pattern similar to that seen after oral and intravenous administration. The elimination half-life was also similar in both g;-ups. Therefore, disposition is similar after eil tier oral or jejunal paracetamol administration. Similar findings were seen after intrajejunal instillation of 5-aminosalicylic acid compared to oral medication (Nielsen & Bondesen, 1983). On the contrary, Magnusson (1983) found an alteration in digoxin metabolism after jejunal instillation when compared to oral administration. Based on these findings, paracetamol administration via jejunostomy tube may be an acceptable route of administration for patients in whom this is the most appropriate access to their gastrointestinal tract.
This work was supported in part by USPHS grant AM 33479 and MH 34223.

Nelson, E. B. & Levitt, J. R. (1980). Aspirin absorption from a feeding jejunostomy. J. Am. Geriatr. Soc., 28, 556-557. Nielsen, 0. H. & Bondesen, S. (1983). Kinetics of 5aminosalicylic acid after jejunal instillation in man. Br. J. clin. Pharmac., 16, 738-740. Magnusson, J. 0. (1983). Metabolism of digoxin after oral and intrajejunal administration. Br. J. clin. Pharmac., 16, 741-742.

(Received 18 November 1985, accepted 4 March 1986)