Case
Report
Nortriptyline Absorption in Short Bowel Syndrome JOYCE E. BROYLES, PHARM.D., REX O. BROWN, PHARM.D., TIMOTHY H. SELF, PHARM.D., RANDALL C. FREDERICK, M.D., AND R. WAYNE LUTHER, M.D. From the
Department of Clinical Pharmacy, Surgery, and Medicine, University of Tennessee, Memphis,
Tennessee
ABSTRACT. Severe short bowel syndrome usually requires a period of parenteral nutrition support until gastrointestinal hypertrophy occurs. Because of the shortened length of the gastrointestinal tract, oral drug therapy can be compromised secondary to decreased absorption. In the case presented, a
patient with short bowel syndrome who required parenteral nutrition was able to achieve therapeutic nortriptyline serum concentrations while receiving the drug via the oral route. (Journal of Parenteral and Enteral Nutrition 14:326-327,1990)
Short bowel syndrome (SBS) was nearly always fatal before the advent of parenteral nutrition. Now that such patients can be supported for indefinite periods with parenteral nutrition, the issue of chronic oral drug therapy in a shortened gastrointestinal tract has become important. To date, absorption of only a few drugs have been studied in SBS patients.I-5 Because patients with severe SBS usually have chronic disease and require parenteral nutrition, they often suffer anxiety and/or depression due to frequent hospitalizations, loss of jobs, and added responsibilities for care of catheters and infusion pumps. Tricyclic antidepressants have been reported to be used in patients with SBS requiring parenteral nutrition with some success,’ but to our knowledge, serum concentrations of these drugs have not been reported. We report a case of presumed adequate oral absorption of nortriptyline in a patient with SBS resulting from multiple small bowel resections to control bleeding from gastrointestinal venous ectasias. Therapeutic nortriptyline concentrations with relief of symptoms were achieved in this patient with a markedly reduced absorptive surface area.
5 to 6 feet of small intestine and 40 to 50 cm of colon remaining and had been maintained on home parenteral nutrition for 2 years (Table I). Within 24 hr of admission, the patient had stopped bleeding; however, blood cultures taken on admission from both peripheral vein and from the double-lumen Hickman catheter (Davol, Inc, Cranston, RI) were posi-
CASE REPORT
A
27-year-old female with a 31/2-year history of numerectasias of the alimentary tract, necessitating numerous hospitalizations and operative procedures for
ous venous
removal of ischemic or necrotized bowel and colon, was admitted to a university hospital with a chief complaint of abdominal pain, cramping and hematochezia. Five days before this admission she was hospitalized for evaluation of a left lower abdominal ecchymosis which was not surgically removed. The patient had approximately
Reprint requests:
Dr. Rex O.
tive for Enterobacter cloacae. The patient was started on 800 mg of vancomycin every 12 hr, and later placed on 75 mg of tobramycin every 8 hr. Surgical exploration of the ecchymosis was planned after the infection subsided. Facing a relatively long hospitalization, the patient became despondent and was started on 100 mg of amitriptyline every night and 50 mg every morning for relief of depressive symptoms. After 6 days of amitriptyline therapy, consultation with the psychiatry service was requested. The patient was switched to 25 mg of nortriptyline every morning and 50 mg every night because she had difficulty in tolerating the anticholinergic side effects of the amitriptyline. Serum nortriptyline concentrations were drawn 30 min before the morning dose at days 6, 15, and 23 of nortriptyline therapy and all were found to be in the therapeutic range (50-140 ng/ml) (Fig. 1). Nortriptyline serum concentrations were determined by gas chromatography. After finishing a 10-day course of antibiotics, blood cultures were negative and the ecchymosis was surgically removed. Her postoperative course was uneventful, except for the appearance of a wound abscess necessitating a second course of iv antibiotics (erythromycin 250 mg every 6 hr). During the course of her hospital stay, there was some improvement in the patient’s mood noted, and further individual psychotherapy was planned after discharge. On day 39 of hospitalization, the patient was discharged. One month after discharge, the patient was readmitted to the hospital because of mechanical problems with her Hickman catheter. A nortriptyline serum concentration measured on the day after admission was 90 ng/ml.
Brown, 26 S. Dunlap. Memphis, TN
38163. 326
Downloaded from pen.sagepub.com at UNIV OF MICHIGAN on June 17, 2015
327 TABLE I
Composition of the parenteral nutrition solution
demonstrated therapeutic digoxin levels in a patient with 15 cm of jejunum. We were unable to locate any previous report of the use of nortriptyline serum concentrations in a patient with SBS, although tricyclic antidepressants have been reported to be used with some success in this 6
patient group.6 Although some controversy does exist about the correlation of serum tricyclic antidepressant concentrations with therapeutic efficacy in depression, it is generally accepted that nortriptyline concentrations within the therapeutic range are associated with clinical improvement.8-10 Nortriptyline, a basic drug with a pKa of 9.73, is almost completely ionized in the stomach. Little is known to date about the site of nortriptyline absorption within the intestinal tract, although absorption most likely occurs in the small bowel. Nortriptyline has been
reported to be about 64% bioavailable in normal subjects a time to peak concentration of 1 hr.11,12 Despite limited surface area, this patient with 5 to 6 feet of small bowel was able to achieve therapeutic serum concentrations on a reasonable oral regimen. Adequate nortriptyline absorption most likely occurred in this patient with short bowel syndrome as evidenced by the therapeutic serum concentrations on successive measurements. Because of the high degree of variability in pharmacokinetic factors which may influence nortriptyline absorption, it is recommended to monwith
*
Clintec Nutrition, Deerfield, IL. t Armour Laboratories, Tuckahoe, NY.
nortriptyline concentrations in SBS patients who receiving this drug. Since this is a single patient observation, further study and clinical observations are itor are
recommended. ’
REFERENCES
FIG. 1. Nortriptyline serum concentrations measured over time in the patient with short bowel syndrome. All measurements were in the therapeutic range established for this drug (50-140 ng/ml).
DISCUSSION
length of the normal human small bowel is not precisely known, however, resection of more than 100 cm of terminal ileum, is usually associated with a significant malabsorption syndrome.’ Several factors limit drug absorption in short bowel syndrome, chief among these being decreased luminal surface area and decreased transit time. Other factors which may influence drug absorption is the amount of intestinal adaptation present, ileocecal valve function (if present), pH of the gastrointestinal contents, and condition of the other digesThe
tive organs. Literature with regard to drug absorption in short bowel syndrome is somewhat limited. Felser and Hui1 described therapeutic procainamide levels in a patient with 26 cm of viable small bowel. Another report described adequate oral absorption of warfarin sodium in a patient with 100 cm of small intestine.2 Veticaden et a13
1. Felser J, Hui K: Procainamide absorption in short bowel syndrome. JPEN 7:154-155, 1983 2. Kearns P, O’Reilly R: Bioavailability of warfarin in a patient with severe short bowel syndrome. JPEN 10:100-101, 1986 3. Vetticaden S, Lehman ME, Barnhart GR, et al: Digoxin absorption in a patient with short-bowel syndrome. Clin Pharm 5:62-64, 1986 4. Krausz MM, Berry E, Freund U: Absorption of orally administered digoxin after massive resection of the small bowel. Am J Gastroenterol 71:220-223, 1979 5. Lehman ME, Kolb KW, Barnhart GR, et al: Warfarin absorption in a patient with short-bowel syndrome. Clin Pharm 4:325-326, 1985 6. Gulledge AD, Gipson WT, Steiger E, et al: Home parenteral nutrition for the short bowel syndrome. Psychological issues. Gen Hosp Psychiat 2:271-281, 1980 7. Urban E: Metabolic consequence of small bowel resection: Short bowel syndrome. Gastroenterology 77:572-579, 1979 8. Asberg M, Cronholm B, Sjoqrist F, et al: Relationship between plasma level and therapeutic effect of nortriptyline. Br Med J
3:331-334, 1971 9.
Kragh-Sorensen P: The relationship between nortriptyline plasma
10.
Kragh-Sorensen P, Asberg M, Eggert-Hansen C, et al: Plasma nortriptyline levels in endogenous depression. Lancet 1:113-115,
levels and clinical effects. Proc Roy Soc Med 68:99-104, 1975
1973 11. Alexanderson
B, Borga 0, Alvan G, et al: The availability of orally administered nortriptyline. Eur J Clin Pharmacol 5:181-185, 1973 12. Gibaldi M: Comparison of observed and predicted bioavailability of nortriptyline in humans following oral administration. J Pharm Sci 64:1036-1037, 1975
Downloaded from pen.sagepub.com at UNIV OF MICHIGAN on June 17, 2015
Report
Nortriptyline Absorption in Short Bowel Syndrome JOYCE E. BROYLES, PHARM.D., REX O. BROWN, PHARM.D., TIMOTHY H. SELF, PHARM.D., RANDALL C. FREDERICK, M.D., AND R. WAYNE LUTHER, M.D. From the
Department of Clinical Pharmacy, Surgery, and Medicine, University of Tennessee, Memphis,
Tennessee
ABSTRACT. Severe short bowel syndrome usually requires a period of parenteral nutrition support until gastrointestinal hypertrophy occurs. Because of the shortened length of the gastrointestinal tract, oral drug therapy can be compromised secondary to decreased absorption. In the case presented, a
patient with short bowel syndrome who required parenteral nutrition was able to achieve therapeutic nortriptyline serum concentrations while receiving the drug via the oral route. (Journal of Parenteral and Enteral Nutrition 14:326-327,1990)
Short bowel syndrome (SBS) was nearly always fatal before the advent of parenteral nutrition. Now that such patients can be supported for indefinite periods with parenteral nutrition, the issue of chronic oral drug therapy in a shortened gastrointestinal tract has become important. To date, absorption of only a few drugs have been studied in SBS patients.I-5 Because patients with severe SBS usually have chronic disease and require parenteral nutrition, they often suffer anxiety and/or depression due to frequent hospitalizations, loss of jobs, and added responsibilities for care of catheters and infusion pumps. Tricyclic antidepressants have been reported to be used in patients with SBS requiring parenteral nutrition with some success,’ but to our knowledge, serum concentrations of these drugs have not been reported. We report a case of presumed adequate oral absorption of nortriptyline in a patient with SBS resulting from multiple small bowel resections to control bleeding from gastrointestinal venous ectasias. Therapeutic nortriptyline concentrations with relief of symptoms were achieved in this patient with a markedly reduced absorptive surface area.
5 to 6 feet of small intestine and 40 to 50 cm of colon remaining and had been maintained on home parenteral nutrition for 2 years (Table I). Within 24 hr of admission, the patient had stopped bleeding; however, blood cultures taken on admission from both peripheral vein and from the double-lumen Hickman catheter (Davol, Inc, Cranston, RI) were posi-
CASE REPORT
A
27-year-old female with a 31/2-year history of numerectasias of the alimentary tract, necessitating numerous hospitalizations and operative procedures for
ous venous
removal of ischemic or necrotized bowel and colon, was admitted to a university hospital with a chief complaint of abdominal pain, cramping and hematochezia. Five days before this admission she was hospitalized for evaluation of a left lower abdominal ecchymosis which was not surgically removed. The patient had approximately
Reprint requests:
Dr. Rex O.
tive for Enterobacter cloacae. The patient was started on 800 mg of vancomycin every 12 hr, and later placed on 75 mg of tobramycin every 8 hr. Surgical exploration of the ecchymosis was planned after the infection subsided. Facing a relatively long hospitalization, the patient became despondent and was started on 100 mg of amitriptyline every night and 50 mg every morning for relief of depressive symptoms. After 6 days of amitriptyline therapy, consultation with the psychiatry service was requested. The patient was switched to 25 mg of nortriptyline every morning and 50 mg every night because she had difficulty in tolerating the anticholinergic side effects of the amitriptyline. Serum nortriptyline concentrations were drawn 30 min before the morning dose at days 6, 15, and 23 of nortriptyline therapy and all were found to be in the therapeutic range (50-140 ng/ml) (Fig. 1). Nortriptyline serum concentrations were determined by gas chromatography. After finishing a 10-day course of antibiotics, blood cultures were negative and the ecchymosis was surgically removed. Her postoperative course was uneventful, except for the appearance of a wound abscess necessitating a second course of iv antibiotics (erythromycin 250 mg every 6 hr). During the course of her hospital stay, there was some improvement in the patient’s mood noted, and further individual psychotherapy was planned after discharge. On day 39 of hospitalization, the patient was discharged. One month after discharge, the patient was readmitted to the hospital because of mechanical problems with her Hickman catheter. A nortriptyline serum concentration measured on the day after admission was 90 ng/ml.
Brown, 26 S. Dunlap. Memphis, TN
38163. 326
Downloaded from pen.sagepub.com at UNIV OF MICHIGAN on June 17, 2015
327 TABLE I
Composition of the parenteral nutrition solution
demonstrated therapeutic digoxin levels in a patient with 15 cm of jejunum. We were unable to locate any previous report of the use of nortriptyline serum concentrations in a patient with SBS, although tricyclic antidepressants have been reported to be used with some success in this 6
patient group.6 Although some controversy does exist about the correlation of serum tricyclic antidepressant concentrations with therapeutic efficacy in depression, it is generally accepted that nortriptyline concentrations within the therapeutic range are associated with clinical improvement.8-10 Nortriptyline, a basic drug with a pKa of 9.73, is almost completely ionized in the stomach. Little is known to date about the site of nortriptyline absorption within the intestinal tract, although absorption most likely occurs in the small bowel. Nortriptyline has been
reported to be about 64% bioavailable in normal subjects a time to peak concentration of 1 hr.11,12 Despite limited surface area, this patient with 5 to 6 feet of small bowel was able to achieve therapeutic serum concentrations on a reasonable oral regimen. Adequate nortriptyline absorption most likely occurred in this patient with short bowel syndrome as evidenced by the therapeutic serum concentrations on successive measurements. Because of the high degree of variability in pharmacokinetic factors which may influence nortriptyline absorption, it is recommended to monwith
*
Clintec Nutrition, Deerfield, IL. t Armour Laboratories, Tuckahoe, NY.
nortriptyline concentrations in SBS patients who receiving this drug. Since this is a single patient observation, further study and clinical observations are itor are
recommended. ’
REFERENCES
FIG. 1. Nortriptyline serum concentrations measured over time in the patient with short bowel syndrome. All measurements were in the therapeutic range established for this drug (50-140 ng/ml).
DISCUSSION
length of the normal human small bowel is not precisely known, however, resection of more than 100 cm of terminal ileum, is usually associated with a significant malabsorption syndrome.’ Several factors limit drug absorption in short bowel syndrome, chief among these being decreased luminal surface area and decreased transit time. Other factors which may influence drug absorption is the amount of intestinal adaptation present, ileocecal valve function (if present), pH of the gastrointestinal contents, and condition of the other digesThe
tive organs. Literature with regard to drug absorption in short bowel syndrome is somewhat limited. Felser and Hui1 described therapeutic procainamide levels in a patient with 26 cm of viable small bowel. Another report described adequate oral absorption of warfarin sodium in a patient with 100 cm of small intestine.2 Veticaden et a13
1. Felser J, Hui K: Procainamide absorption in short bowel syndrome. JPEN 7:154-155, 1983 2. Kearns P, O’Reilly R: Bioavailability of warfarin in a patient with severe short bowel syndrome. JPEN 10:100-101, 1986 3. Vetticaden S, Lehman ME, Barnhart GR, et al: Digoxin absorption in a patient with short-bowel syndrome. Clin Pharm 5:62-64, 1986 4. Krausz MM, Berry E, Freund U: Absorption of orally administered digoxin after massive resection of the small bowel. Am J Gastroenterol 71:220-223, 1979 5. Lehman ME, Kolb KW, Barnhart GR, et al: Warfarin absorption in a patient with short-bowel syndrome. Clin Pharm 4:325-326, 1985 6. Gulledge AD, Gipson WT, Steiger E, et al: Home parenteral nutrition for the short bowel syndrome. Psychological issues. Gen Hosp Psychiat 2:271-281, 1980 7. Urban E: Metabolic consequence of small bowel resection: Short bowel syndrome. Gastroenterology 77:572-579, 1979 8. Asberg M, Cronholm B, Sjoqrist F, et al: Relationship between plasma level and therapeutic effect of nortriptyline. Br Med J
3:331-334, 1971 9.
Kragh-Sorensen P: The relationship between nortriptyline plasma
10.
Kragh-Sorensen P, Asberg M, Eggert-Hansen C, et al: Plasma nortriptyline levels in endogenous depression. Lancet 1:113-115,
levels and clinical effects. Proc Roy Soc Med 68:99-104, 1975
1973 11. Alexanderson
B, Borga 0, Alvan G, et al: The availability of orally administered nortriptyline. Eur J Clin Pharmacol 5:181-185, 1973 12. Gibaldi M: Comparison of observed and predicted bioavailability of nortriptyline in humans following oral administration. J Pharm Sci 64:1036-1037, 1975
Downloaded from pen.sagepub.com at UNIV OF MICHIGAN on June 17, 2015
