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References
1. Westrin P. Intravenous and inhalational anaesthetic agents.
Baillie`res Clin Anaesthesiol 1996;10:687715.
2. Anonymous. Sevoflurane and desflurane: comparison with
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3. Eger EI 2nd. Desflurane animal and human pharmacology:
aspects of kinetics, safety, and MAC. Anesth Analg
1992;75(Suppl 4):S39.
4. Song D, Joshi GP, White PF. Fast-track eligibility after
ambulatory anesthesia: a comparison of desflurane,
sevoflurane, and propofol. Anesth Analg 1998;86(2):26773.
5. Rodig G, Wild K, Behr R, Hobbhahn J. Effects of desflurane and isoflurane on systemic vascular resistance during
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Anesth 1997;11(1):547.
6. Warltier DC, Pagel PS. Cardiovascular and respiratory
actions of desflurane: is desflurane different from isoflurane? Anesth Analg 1992;75(Suppl 4):S1731.
7. Bunting HE, Kelly MC, Milligan KR. Effect of nebulized
lignocaine on airway irritation and haemodynamic changes
during induction of anaesthesia with desflurane. Br J
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8. Bennett JA, Lingaraju N, Horrow JC, McElrath T,
Keykhah MM. Elderly patients recover more rapidly from
desflurane than from isoflurane anesthesia. J Clin Anesth
1992;4(5):37881.
9. Zwass MS, Fisher DM, Welborn LG, Cote CJ, Davis PJ,
Dinner M, Hannallah RS, Liu LM, Sarner J, McGill WA,
et al Induction and maintenance characteristics of
anesthesia with desflurane and nitrous oxide in infants
and children. Anesthesiology 1992;76(3):3738.
10. Ornstein E, Young WL, Fleischer LH, Ostapkovich N.
Desflurane and isoflurane have similar effects on cerebral
blood flow in patients with intracranial mass lesions.
Anesthesiology 1993;79(3):498502.
11. Kelly RE, Lien CA, Savarese JJ, Belmont MR,
Hartman GS, Russo JR, Hollmann C. Depression of neuromuscular function in a patient during desflurane anesthesia.
Anesth Analg 1993;76(4):86871.
12. Weiskopf RB, Eger EI 2nd, Ionescu P, Yasuda N,
Cahalan MK, Freire B, Peterson N, Lockhart SH,
Rampil IJ, Laster M. Desflurane does not produce hepatic
or renal injury in human volunteers. Anesth Analg
1992;74(4):5704.
13. Berghaus TM, Baron A, Geier A, Lamerz R,
Paumgartner G, Conzen P. Hepatotoxicity following desflurane anesthesia. Hepatology 1999;29(2):61314.
14. Annila P, Rorarius M, Reinikainen P, Oikkonen M, Baer G.
Effect of pre-treatment with intravenous atropine or
glycopyrrolate on cardiac arrhythmias during halothane
anaesthesia for adenoidectomy in children. Br J Anaesth
1998;80(6):75660.
15. Fu ES, Scharf JE, Mangar D, Miller WD. Malignant
hyperthermia involving the administration of desflurane.
Can J Anaesth 1996;43(7):68790.
16. Gold MI, Abello D, Herrington C. Minimum alveolar
concentration of desflurane in patients older than 65 yr.
Anesthesiology 1993;79(4):71014.
17. Moore MA, Weiskopf RB, Eger EI 2nd, Wilson C, Lu G.
Arrhythmogenic doses of epinephrine are similar during
desflurane
or
isoflurane
nesthesia
in
humans.
Anesthesiology 1993;79(5):9437.
18. Sebel PS, Glass PS, Fletcher JE, Murphy MR, Gallagher C,
Quill T. Reduction of the MAC of desflurane with fentanyl.
Anesthesiology 1992;76(1):529.
19. Eriksson H, Korttila K. Recovery profile after desflurane
with or without ondansetron compared with propofol in
2006 Elsevier B.V. All rights reserved.
Desloratadine
See also Antihistamines
General Information
Desloratadine is the primary metabolite of loratadine,
with superior H1 receptor binding, potent antihistaminic
activity compared with the parent compound, and proven
efficacy in allergic disease (1). It is effective and well
tolerated in seasonal allergic rhinitis, including relief of
nasal congestion (24).
In a randomized, open, four-way, crossover study in 20
healthy men desloratadine was given as single doses (5,
7.5, 10, and 20 mg) in four different treatment periods
with 14 days between each dose. The Cmax for all doses
occurred at 4 hours after administration, with a half-life of
2124 hours. There were no dose-related differences in
drug absorption rate, and even the 20 mg dose was well
tolerated (5). The systemic availability of desloratadine
was unaffected by food in healthy adult volunteers (6).
Nervous system
Desloratadine appears to be minimally sedative, given
that several studies, published in abstract, have shown
no impairment in terms of wakefulness or psychomotor
performance (1012). Moreover, in a study in which
desloratadine was effective and well tolerated in patients
with seasonal allergic rhinitis there were no clinically
significant sedative effects (7).
Desloratadine
1075
Psychological, psychiatric
Ketoconazole
The electrocardiographic safety of desloratadine in combination with the CYP3A4 inhibitor ketoconazole has
been assessed in a randomized, two-way, crossover,
third-party-blind, multiple-dose, placebo-controlled
study over 10 days in 24 healthy volunteers (21).
Compared with desloratadine alone there were no significant or clinically important changes in QTc, QT,
PR, or QRS intervals when desloratadine (7.5 mg/day,
that is 50% higher than the recommended dose) was
co-administered with ketoconazole (200 mg bd). There
was a 1.3-fold increase in desloratadine Cmax when it
was co-administered with ketoconazole, but this was
judged not to be clinically important. The authors concluded that co-administration of desloratadine with
ketoconazole has no clinically relevant electrocardiographic or pharmacodynamic implications. There was
no clinically relevant interaction between desloratadine
and ketoconazole (21).
Susceptibility Factors
Genetic factors
The effect of race on desloratadine pharmacokinetics at
steady state has been examined (16). The authors concluded that no dosage adjustments for desloratadine were
required.
Age
The effect of age on desloratadine pharmacokinetics at
steady state has been examined (17). The authors concluded that no dosage adjustments for desloratadine were
required.
Sex
The effect of sex on desloratadine pharmacokinetics at
steady state has been examined (16). The authors concluded that no dosage adjustments for desloratadine were
required.
DrugDrug Interactions
Azithromycin
The effect of co-administration of azithromycin on
plasma concentrations of desloratadine has been
examined in a randomized third-party-blind, placebocontrolled, parallel-group study in 90 healthy volunteers (18). An initial loading dose of azithromycin
(500 mg) was given on day 3, followed by 250 mg od
for 4 days. Concomitant azithromycin had little effect
(<15%) on either the Cmax or AUC of desloratadine,
and there were no statistically significant increases in
the PR, QT, QTc interval, QRS complex duration, or
ventricular rate after administration of desloratadine
with or without azithromycin.
Erythromycin
There was no clinically relevant interaction between
desloratadine and erythromycin (9).
Fluoxetine
Co-administration of desloratadine with fluoxetine did
not result in clinically relevant changes in the pharmacokinetics of either drug in 54 healthy volunteers (19).
Grapefruit juice
In an unblinded, randomized, single-dose, crossover study
in 24 healthy adults, grapefruit juice had no effect on the
systemic availability of oral desloratadine (20). There
were no clinically significant electrocardiographic
changes after co-administration of grapefruit juice with
desloratadine compared with desloratadine alone.
2006 Elsevier B.V. All rights reserved.
References
1. McClellan K, Jarvis B. Desloratadine. Drugs 2001;
61(6):78996.
2. Horak F, Stubner UP, Zieglmayer R, Ing D, Harris AG.
Effect of desloratadine versus placebo on nasal airflow and
subjective measures of nasal obstruction in subjects with
grass pollen-induced allergic rhinitis in an allergen-exposure
unit. J Allergy Clin Immunol 2002;109(6):95661.
3. Bachert C, Virchow CJ Jr, Plenker A. Desloratadine in the
treatment of seasonal allergic rhinitis: results of a large
observational study. Clin Drug Invest 2002;22:4352.
4. Wilson AM, Haggart K, Sims EJ, Lipworth BJ. Effects of
fexofenadine and desloratadine on subjective and objective
measures of nasal congestion in seasonal allergic rhinitis.
Clin Exp Allergy 2002;32(10):15049.
5. Gupta S, Banfield C, Affrime M, Marco A, Cayen M,
Herron J, Padhi D. Desloratadine demonstrates dose proportionality in healthy adults after single doses. Clin
Pharmacokinet 2002;41(Suppl 1):16.
6. Gupta S, Banfield C, Affrime M, Marbury T, Padhi D,
Glue P. Oral bioavailability of desloratadine is unaffected
by food. Clin Pharmacokinet 2002;41(Suppl 1):712.
7. Meltzer EO, Prenner BM, Nayak A; The Desloratadine
Study Group. Efficacy and tolerability of once-daily
5 mg desloratadine, an H1-receptor antagonist, in patients
with seasonal allergic rhinitis: assessment during the spring
and fall allergy seasons. Clin Drug Invest 2001;21:2532.
8. Ring J, Hein R, Gauger A, Bronsky E, Miller B,
Breneman D, Conneley M, Corren J, Ceuppens J,
Fierlbeck G, Friday G, Goldberg P, Graft D, Holst T,
Honsinger R, Hornmark A-M, Kaiser H, Kaplan R,
Kempers S, Lockey R, Miller SD, Nayak A, Nayak N,
Pariser D, Prenner B, Ruzicka T, Stewart GE II,
Thompson M, Wein M. Once-daily desloratadine improves
the signs and symptoms of chronic idiopathic urticaria: a
randomized, double-blind, placebo-controlled study. Int J
Dermatol 2001;40(1):726.
9. Banfield C, Hunt T, Reyderman L, Statkevich P, Padhi D,
Affrime M. Lack of clinically relevant interaction between
desloratadine and erythromycin. Clin Pharmacokinet
2002;41(Suppl 1):2935.
10. Scharf MB, Kay GC, Rikken G, Danzig MR, Staudinger H.
Desloratadine has no effect on wakefulness or psychomotor
performance. Allergy 2000;55(Suppl 63):Abstract 280.
1076 Desmopressin
11. Vuurman E, Ramaekers JG, Rikken G, De Halleux F.
Desloratadine does not impair actual driving performance:
a three way crossover comparison with diphenhydramine
and placebo. Allergy 2000;55(Suppl 63):Abstract 263.
12. Valk PJL, Van Roon DB, Simons M, Rikken G, Lether IC,
Staudinger H. No impairment of flying ability with desloratadine use in healthy volunteers under conditions of simulated cabin pressure. Allergy 2001;56(Suppl 68):Abstract
229.
13. Wilken JA, Kane RL, Ellis AK, Rafeiro E, Briscoe MP,
Sullivan CL, Day JH. A comparison of the effect of diphenhydramine and desloratadine on vigilance and cognitive
function during treatment of ragweed-induced allergic rhinitis. Ann Allergy Asthma Immunol 2003;91(4):37585.
14. Nicholson AN, Handford AD, Turner C, Stone BM. Studies
on performance and sleepiness with the H1-antihistamine,
desloratadine. Aviat Space Environ Med 2003;74(8):80915.
15. Valk PJ, Van Roon DB, Simons RM, Rikken G.
Desloratadine shows no effect on performance during 6 h
at 8,000 ft simulated cabin altitude. Aviat Space Environ
Med 2004;75(5):4338.
16. Affrime M, Banfield C, Gupta S, Cohen A, Boutros T,
Thonoor M, Cayen M. Effect of race and sex on single and
multiple dose pharmacokinetics of desloratadine. Clin
Pharmacokinet 2002;41(Suppl 1):218.
17. Affrime M, Gupta S, Banfield C, Cohen A. A pharmacokinetic profile of desloratadine in healthy adults, including
elderly. Clin Pharmacokinet 2002;41(Suppl 1):1319.
18. Gupta S, Banfield C, Kantesaria B, Marino M, Clement R,
Affrime M, Batra V. Pharmacokinetic and safety profile of
desloratadine and fexofenadine when coadministered with
azithromycin: a randomized, placebo-controlled, parallelgroup study. Clin Ther 2001;23(3):45166.
19. Gupta S, Banfield C, Kantesaria B, Flannery B, Herron J.
Pharmacokinetics/pharmacodynamics of desloratadine and
fluoxetine in healthy volunteers. J Clin Pharmacol
2004;44(11):12529.
20. Banfield C, Gupta S, Marino M, Lim J, Affrime M.
Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine. Clin Pharmacokinet
2002;41(4):31118.
21. Banfield C, Herron J, Keung A, Padhi D, Affrime M.
Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole. Clin Pharmacokinet 2002;41(Suppl 1):3744.
Desmopressin
See also Vasopressin and analogues
General Information
Desmopressin (N-deamino-8-D-arginine vasopressin,
dDAVP) is a longer acting analogue of vasopressin. It has
very little vasoactive effect but is antidiuretic by an
action on vasopressin V2 receptors in the renal tubule
and is used to treat central diabetes insipidus and nocturnal enuresis.
At higher doses desmopressin also has significant
hematological effects and can significantly boost concentrations of factor VIII and von Willebrand factor (VWF)
in the blood. Desmopressin is therefore a valuable agent
for the treatment of mild and moderate hemophilia
2006 Elsevier B.V. All rights reserved.