Page last updated: 2024-11-04

dihydrocodeine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

dihydrocodeine: RN refers to parent cpd(5alpha,6alpha)-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID5284543
CHEMBL ID1595
CHEBI ID135276
SCHEMBL ID24607
MeSH IDM0063004

Synonyms (59)

Synonym
(5alpha,6alpha)-17-methyl-3-(methyloxy)-4,5-epoxymorphinan-6-ol
alpha-hydrocodol
6-alpha-hydrocodol
3-methoxy-12-methyl-5,6,7,7a,8,9-hexahydro-4ah-8,9c-iminoethanophenanthro(4,5-bcd)furan-5-ol
morphinan-6alpha-ol, 4,5alpha-epoxy-3-methoxy-17-methyl-
dihydrocodeine [inn:ban]
einecs 204-732-3
6alpha-hydrocodol
8,14-dihydroneopine
diidrocodeina [dcit]
codeine, 7,8-dihydro-
morphinan-6-ol, 4,5-epoxy-3-methoxy-17-methyl-, (5alpha,6alpha)-
hydrocodeine
dea no. 9120
dihidrocodeina [inn-spanish]
dihydrokodein [czech]
dihydrocodeinum [inn-latin]
morphinan-6-alpha-ol, 4,5-alpha-epoxy-3-methoxy-17-methyl-
DB01551
125-28-0
dihydrocodeine
codhydrine
dehacodin
rapacodin
novicondin
nsc-231319
CHEBI:135276
D07831
dihydrocodeine (inn)
remedacen (tn)
ids-nd-008(sect.2)
remedacen
dh-codeine
.alpha.-hydrocodol
CHEMBL1595
dihidrocodeina
dihydrocodeinum
dihydrocodeine [inn]
diidrocodeina
n9i9hdb855 ,
unii-n9i9hdb855
morphinan-6-ol, 4,5-epoxy-3-methoxy-17-methyl-
dihydrocodeine [who-dd]
dihydrocodeine [mart.]
dihydrocodeine [vandf]
hydrocodone hydrogen tartrate 2.5-hydrate impurity b [ep impurity]
dihydrocodeine [mi]
gtpl7594
dicogesic
paracodeine
(4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol
SCHEMBL24607
RBOXVHNMENFORY-DNJOTXNNSA-N
DTXSID5022936
dihydrocodein
Q377270
(4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
(4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,3,4,4a,5,6,7,7a-octahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
morphinan-6-ol, 4,5-epoxy-3-methoxy-17-methyl-, (5?,6?)-

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence."( Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer.
Barni, S; Daffonchio, L; Luporini, G; Marchi, E, 1998
)
0.3
" As the drug is commonly available appropriate titration and dosing and knowledge of its metabolism and possible adverse effects are important for safe prescription of DHC."( Dihydrocodeine: safety concerns.
Leppert, W; Woroń, J, 2016
)
0.43
"Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic."( Relative toxicity of analgesics commonly used for intentional self-poisoning: A study of case fatality based on fatal and non-fatal overdoses.
Bankhead, C; Casey, D; Clements, C; Ferrey, A; Fuller, A; Geulayov, G; Gunnell, D; Hawton, K; Kapur, N; Ness, J; Wells, C, 2019
)
0.51

Pharmacokinetics

Dihydrocodeine concentrations at the effect site were obtained by convolution of a first-order transfer function with the function describing the plasma concentration versus time courses. Miotic effects were related to effect-site concentrations by a sigmoidal pharmacodynamic model. In contrast to the rapid clearance of dihydro codeine from blood in the 14-year-old girl (apparent half-life of 3 hours), the 1-month-old baby boy still had high serum concentrations.

ExcerptReferenceRelevance
"8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration."( The effect of ageing on the pharmacokinetics of dihydrocodeine.
Castleden, CM; Davies, KN; Jagger, C; McBurney, A, 1989
)
0.28
"To determine whether age-dependent pharmacokinetic and pharmacodynamic alterations account for a more pronounced response to benzodiazepines among elderly patients."( Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction.
Dilger, K; Klotz, U; Mikus, G; Platten, HP; Schweizer, E, 1998
)
0.3
"Elderly patients are more sensitive to the sedative action of midazolam than young patients, and the sensitivity is caused by age-dependent pharmacodynamic alterations."( Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction.
Dilger, K; Klotz, U; Mikus, G; Platten, HP; Schweizer, E, 1998
)
0.3
" Dihydrocodeine concentrations at the effect site were obtained by convolution of a first-order transfer function with the function describing the plasma concentration versus time courses, and miotic effects were related to effect-site concentrations by a sigmoidal pharmacodynamic model."( Pharmacokinetic-pharmacodynamic modeling of the miotic effects of dihydrocodeine in humans.
Lötsch, J; Schmidt, H, 2007
)
0.34
" The transfer half-life between plasma and effect site was 21."( Pharmacokinetic-pharmacodynamic modeling of the miotic effects of dihydrocodeine in humans.
Lötsch, J; Schmidt, H, 2007
)
0.34
"Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available."( Applications of minimal physiologically-based pharmacokinetic models.
Cao, Y; Jusko, WJ, 2012
)
0.38
" The developed and validated method was successfully applied to a pharmacokinetic study of AAP (500mg) with DHC (20mg) capsule in Chinese healthy volunteers (N=20)."( Simultaneous determination of acetaminophen and dihydrocodeine in human plasma by UPLC-MS/MS: Its pharmacokinetic application.
Gao, P; Liu, Z; Lou, D; Qiu, X; Su, D; Zhang, NS, 2015
)
0.42
" The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of DHC in healthy Chinese volunteers after oral administration."( UPLC-MS-MS Determination of Dihydrocodeine in Human Plasma and Its Application to a Pharmacokinetic Study.
Duan, YP; Li, W; Qiu, JF; Zhang, WM; Zhang, ZY, 2016
)
0.43
" In contrast to the rapid clearance of dihydrocodeine from blood in the 14-year-old girl (apparent half-life of 3 hours), the 1-month-old baby boy still had high serum concentrations of dihydrocodeine (400 nmol/L) and dihydromorphine (1."( Dihydrocodeine Overdoses in a Neonate and in a 14-year-old Girl Who Were Both Genotyped as Cytochrome P450 2D6*1/*10-*36: Comparing Developmental Ages and Drug Monitoring Data With the Results of Pharmacokinetic Modeling.
Fukuoka, T; Kondo, T; Shimizu, M; Tanaka, T; Yamazaki, H, 2018
)
0.48

Compound-Compound Interactions

ExcerptReferenceRelevance
" The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine (0."( Drug interactions in the reinforcing effects of over-the-counter cough syrups.
Masukawa, Y; Misawa, M; Suzuki, T, 1990
)
0.28
"Auricular point sticking before operation combined with conventional western medicine with oral administration for preventing and treating postoperative complications of external excision and internal ligation on mixed hemorrhoid achieves positive and reliable efficacy."( [Clinical observation of auricular point sticking combined with western medicine for preventing and treating postoperative complications of external excision and internal ligation on mixed hemorrhoid].
Li, J; Long, Q; Wen, Y, 2015
)
0.42

Bioavailability

ExcerptReferenceRelevance
" These methods have been used to compare the bioavailability in four subjects of a controlled-release formulation of dihydrocodeine bitartrate (equivalent to 90 mg of base) with that of a solution (equivalent to 3 x 30 mg of base)."( Two assays for dihydrocodeine in plasma and in urine and their use to determine the bioavailability of a controlled-release product.
Cowan, DA; Noormohammadi, A; Woffendin, G, 1988
)
0.27
" From the AUC, the mean bioavailability of orally administered drug was 21% (range 12-34%)."( Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites.
Rawlins, MD; Rowell, FJ; Seymour, RA, 1983
)
0.27

Dosage Studied

Zomepirac was statistically better than dihydrocodeine in the multiple dosing phase. Concurrent dosing of dihydROcodeine and ebastine produced a significant place preference. On the other hand, concurrent dosing with methylephedrine (4 mg/kg) and a mixture (SC) of caffeine (4mg/kg), chlorpheniramine (0.5mg/ kg) produced a positive effect.

ExcerptRelevanceReference
" Tolerance in terms of withdrawals or side-effect profile did not appear to the dosage of each preparation administered."( The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hips.
Costello, F; Eves, MJ; James, IG; Lloyd, RS; Miller, AJ, 1992
)
0.28
" On the other hand, concurrent dosing of dihydrocodeine (2 mg/kg, IP) and a mixture (SC) of methylephedrine (4 mg/kg), caffeine (4 mg/kg) and chlorpheniramine (0."( Drug interactions in the reinforcing effects of over-the-counter cough syrups.
Masukawa, Y; Misawa, M; Suzuki, T, 1990
)
0.28
"8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration."( The effect of ageing on the pharmacokinetics of dihydrocodeine.
Castleden, CM; Davies, KN; Jagger, C; McBurney, A, 1989
)
0.28
" In the multiple dosing phase, zomepirac was statistically better than dihydrocodeine."( Zomepirac, dihydrocodeine and placebo compared in postoperative pain after day-case surgery. The relationship between the effects of single and multiple doses.
Bullingham, RE; Carroll, D; Collin, J; Evans, PJ; Lloyd, JW; McQuay, HJ; Moore, RA; O'Sullivan, G, 1985
)
0.27
"The dissolution rate constants of dihydrocodein in two retard drug dosage forms based on synthetic ion exchange resin were determined with four dissolution methods."( [Investigations in Bioavailability of resinates as peroral retard drug dosage forms. Part 1: Pharmaceutical availability of dihydrocodein-resinates (author's transl)].
Glaubitz, H; Mühlenbruch, B; Strauss, H, 1982
)
0.26
" This conclusion must however, be confirmed with repeated dosing in patients with pain."( The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers.
Hufschmid, E; Thormann, W; Wilder-Smith, CH, 1998
)
0.3
" Because of similar metabolic degradation, calculation of the time-dependent ratio of the concentration of morphine and its glucuronide metabolites in blood or serum allows a rough estimation of increased dosage and of time elapsed since the last application."( Formation and clearance of active and inactive metabolites of opiates in humans.
Aderjan, RE; Skopp, G, 1998
)
0.3
" Dose-response relationships show that higher doses of ibuprofen may be particularly effective."( Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review.
McQuay, HJ; Moore, RA, 1998
)
0.3
" Concurrent dosing of dihydrocodeine and ebastine produced a significant place preference."( Effects of second generation of histamine H1 antagonists, cetirizine and ebastine, on the antitussive and rewarding effects of dihydrocodeine in mice.
Kamei, J; Miyata, S; Morita, K; Onodera, K, 2003
)
0.32
" Initial dose of codeine is 60 mg x day(-1) and the dosage should be increased or decreased according to pain intensity, patients' general condition and age."( [Indication and usage of opioids except morphine for chronic non-malignant intractable pain].
Saeki, S, 2008
)
0.35
" In this article pharmacokinetics, pharmacodynamics, dosing guidelines, adverse effects and clinical studies of DHC in pain management are shown with focus on cancer pain."( Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain.
Leppert, W, 2010
)
0.36
" As the drug is commonly available appropriate titration and dosing and knowledge of its metabolism and possible adverse effects are important for safe prescription of DHC."( Dihydrocodeine: safety concerns.
Leppert, W; Woroń, J, 2016
)
0.43
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
morphinane alkaloidAn isoquinoline alkaloid based on a morphinan skeleton and its substituted derivatives.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (31)

Assay IDTitleYearJournalArticle
AID496819Antimicrobial activity against Plasmodium falciparum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1057806Displacement of [3H]DADLE from delta opioid receptor in CHO cells at 10 uM after 120 mins relative to control2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID496823Antimicrobial activity against Trichomonas vaginalis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID476929Human intestinal absorption in po dosed human2010European journal of medicinal chemistry, Mar, Volume: 45, Issue:3
Neural computational prediction of oral drug absorption based on CODES 2D descriptors.
AID496832Antimicrobial activity against Trypanosoma brucei rhodesiense2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID497005Antimicrobial activity against Pneumocystis carinii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1057808Displacement of [3H]diprenorphine from mu opioid receptor in HEK293 cells at 1 uM after 120 mins relative to control2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID496829Antimicrobial activity against Leishmania infantum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496817Antimicrobial activity against Trypanosoma cruzi2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496824Antimicrobial activity against Toxoplasma gondii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1057807Displacement of [3H]diprenorphine from mu opioid receptor in HEK293 cells at 10 uM after 120 mins relative to control2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID1057809Inhibition of UDP-glucuronosyltransferase in Sprague-Dawley rat hepatocytes assessed as morphine conversion to M3G at 5 to 10 uM incubated for 72 hrs prior to substrate addition measured after 2 hrs by HPLC analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID496830Antimicrobial activity against Leishmania major2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496821Antimicrobial activity against Leishmania2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1057805Displacement of [3H]DADLE from delta opioid receptor in CHO cells at 1 uM after 120 mins relative to control2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID409958Inhibition of bovine brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID496825Antimicrobial activity against Leishmania mexicana2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496827Antimicrobial activity against Leishmania amazonensis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496831Antimicrobial activity against Cryptosporidium parvum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1057813Inhibition of UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M6G after 30 mins by HPLC analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID1057803Displacement of [3H]U-69593 from kappa opioid receptor in CHO cells at 10 uM after 120 mins relative to control2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID409960Inhibition of bovine brain MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID496818Antimicrobial activity against Trypanosoma brucei brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID128027Compound was tested for analgesic activity by writhing assay in mouse after subcutaneous administration1981Journal of medicinal chemistry, Jun, Volume: 24, Issue:6
Analgesic narcotic antagonists. 6. 7 beta, 8 beta-Methano- and 7 beta, 8 beta-epoxydihydrocodeinone.
AID1057804Displacement of [3H]U-69593 from kappa opioid receptor in CHO cells at 1 uM after 120 mins relative to control2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID1057814Inhibition of UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G up to 50 uM after 30 mins by HPLC analysis relative to control2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID496828Antimicrobial activity against Leishmania donovani2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496820Antimicrobial activity against Trypanosoma brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID178138Compound was tested for analgesic activity by tail-flick assay in rat after subcutaneous administration1981Journal of medicinal chemistry, Jun, Volume: 24, Issue:6
Analgesic narcotic antagonists. 6. 7 beta, 8 beta-Methano- and 7 beta, 8 beta-epoxydihydrocodeinone.
AID496826Antimicrobial activity against Entamoeba histolytica2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID781325pKa (acid-base dissociation constant) as determined by Liao ref: J Chem Info Model 20092014Pharmaceutical research, Apr, Volume: 31, Issue:4
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (267)

TimeframeStudies, This Drug (%)All Drugs %
pre-199087 (32.58)18.7374
1990's74 (27.72)18.2507
2000's52 (19.48)29.6817
2010's45 (16.85)24.3611
2020's9 (3.37)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials56 (20.36%)5.53%
Reviews17 (6.18%)6.00%
Case Studies34 (12.36%)4.05%
Observational1 (0.36%)0.25%
Other167 (60.73%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Randomized Controlled Double Blind Trial of Short vs Long Acting Dihydrocodeine in Chronic Non-Malignant Pain [NCT00547885]Phase 460 participants (Actual)Interventional2007-10-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]