Solubility and Ionization Characteristics of Doxepin and Desmethyldoxepin

Embil, Koral; Torosian, George

doi:10.1002/jps.2600710213

Cited by 15 publications

(6 citation statements)

References 5 publications

(1 reference statement)

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“…Mean M/P ratio for doxepin was 1.08 before and 1.66 after feeding while mean M/P ratio for N-desmethyldoxepin was 1.02 before and 1.53 after feeding. The increase in concentration of both doxepin and Ndesmethyldoxepin in the milk during feeding is most probably related to the high lipid solubility of these compounds (log hexane water partition coefficient for doxepin = 4.13; Embil & Torosian, 1982) and the marked 4-5 fold increase in lipid content of milk which occurs during feeding (Hall, 1975). The MIP ratios for doxepin and N-desmethyldoxepin are similar to those reported for amitriptyline and nortriptyline (Bader & Newman, 1980) and imipramine and 1.08 ± 0.10 1.66 ± 0.18 1.02 ± 0.10 1.53 ± 0.16 desipramine (Sovner & Orsulak, 1979).…”

Section: Discussionmentioning

confidence: 99%

“…In Western societies, the prevalence of breast feeding, particularly in the first 6 months postpartum, has increased markedly over the past 10 years (Wilson et al, 1980). Doxepin, N-desmethyldoxepin (pKas = 8.96 and 9.75, respectively;Embil & Torosian, 1982) and tricyclic antidepressants in general are all weak bases and as such would be predicted to have milk/plasma (M/P) ratios greater than 1 (Rasmussen, 1973). Thus, the physician wishing to use tricyclic antidepressants to treat postnatal depression in a patient who desires to breast feed her infant is faced with the dilemma of evaluating what effect, if any, such treatment may have on the infant.…”

Section: Introduction Human Milkmentioning

confidence: 99%

See 1 more Smart Citation

Excretion of doxepin and N‐desmethyldoxepin in human milk.

Kemp¹,

Ilett²,

Booth³

et al. 1985

Brit J Clinical Pharma

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Doxepin and N‐desmethyldoxepin concentrations in plasma and breast milk from a lactating mother and in plasma from her infant were measured during an 8 week period using high performance liquid chromatography. Plasma concentrations ranged from 35‐68 microgram l‐1 for doxepin and 65‐131 microgram l‐1 for N‐desmethyldoxepin. Mean pre‐feed milk/plasma ratios were 1.08 and 1.02 for doxepin and N‐desmethyldoxepin respectively and increased to 1.66 and 1.53 at the post‐feed samples. Only N‐desmethyldoxepin (15 microgram l‐1) was detectable in the infant's plasma sampled after 43 days of maternal therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introduction Human Milkmentioning

confidence: 99%

Excretion of doxepin and N‐desmethyldoxepin in human milk.

Kemp¹,

Ilett²,

Booth³

et al. 1985

Brit J Clinical Pharma

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“…The poor extractability could be attributed to the compounds' large volume of distribution (13,14) and sparing water solubility (15). The poor extractability could be attributed to the compounds' large volume of distribution (13,14) and sparing water solubility (15).…”

Section: Discussionmentioning

confidence: 99%

“…Very limited extraction of daxepin (7.6%) and desmethyldoxepin (13.9%) resulted from each single pass of dialysis fluid through the artificial kidney systems. The poor extractability could be attributed to the compounds' large volume of distribution (13,14) and sparing water solubility (15). Assuming a mean volume of distribution of 20 L/kg for doxepin and desmethyldoxepin (13,14), the drug recovery in terms of a fraction of the body store of the compound removed did not exceed 1.0%.…”

Section: Discussionmentioning

confidence: 99%

Hemodialysis of Doxepin and Desmethyldoxepin in Uremic Patients

1984

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The disposition of doxepin and its active metabolite desmethyldoxepin was investigated in five uremic patients undergoing hemodialysis. The hemodialysis system yielded a mean extraction efficiency of 7.6% for doxepin and 13.9% for desmethyldoxepin. Mean dialysis clearances were 10.8 and 18.1 ml/min for doxepin and desmethyldoxepin, respectively. The drug and metabolite recovery constituted a very small fraction of the body store, i.e., less than 1%. Hemodialysis did not significantly alter the plasma half-life of doxepin, 14.6 +/- 4.3 h, or of desmethyldoxepin, 25.4 +/- 5.5 h. The nondialyzability of both compounds could be attributed to the compounds' protein binding and volume of distribution. The dialysis experiments show that modification of the usual dosage regimen is not necessary during hemodialysis or on dialysis days. The dialysis parameters confirm that hemodialysis is not likely to be of value in the management of acute doxepin poisoning.

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“…All measurements were performed at ambient temperature, unless explicitly stated, at pH ∼7 to ensure the protonation of DOX (p K a = 9 (ref. 58)), using rectangular SUPRASIL® quartz glass cuvettes (Hellma Analytics) with 1 cm path length. The 1 : 1 binding constant of BE to CB7 was determined using fluorescence titration with 2 μM BE and different concentrations of CB7.…”

Section: Methodsmentioning

confidence: 99%