Table 2. . Genetic variants affecting the pharmacodynamics and the pharmacokinetics of oxycodone.

Gene	Variant	Effect	Study (year)	Ref.
OPRM1
	rs1799971 (118A>G)	i. Reduced antinociceptive effect exposed to experimental pain ii. Reduced ability to keep focus	Zwisler et al. (2010)	[47]
		No difference in any of the pain measurements or adverse drug reactions in the first 24 h after surgery	Zwisler et al. (2012)	[48]
		Reduced analgesic response to experimental visceral pressure	Olesen et al. (2015)	[49]
		Gene dosage effect with the GG genotype requiring the highest dose	Cajanus et al. (2014)	[50]
		Higher dose in GG compared with the AA and the AG genotypes in patients with cancer pain	Lin et al. (2018)	[51]
	rs589046 (C>T)	Improved analgesic response to experimental skin heat and visceral pressure	Olesen et al. (2015)	[49]
	rs563649 (C>T)	Improved analgesic response to experimental skin heat	Olesen et al. (2015)	[49]
	rs9479757 (G>A)	Improved pain tolerance threshold to experimental visceral pressure	Olesen et al. (2015)	[49]
	rs533586 (C>A/T)	Poor analgesic response to experimental visceral pressure	Olesen et al. (2015)	[49]
OPRD1
	rs419335 (A>G)	Poor analgesic response to experimental visceral heat	Olesen et al. (2015)	[49]
	rs2234918 (C>G/T)	Improved analgesic response to experimental muscle pressure	Olesen et al. (2015)	[49]
ABCB1
	C3435T	Less pronounced adverse drug reactions: nausea/vomiting, tiredness/drowsiness, itching and for the total sum of adverse drug reactions	Zwisler et al. (2010)	[47]
		No difference in any of the pain measurements or adverse drug reactions in the first 24 h after surgery	Zwisler et al. (2012)	[48]
	G2677T/A	i. Variant T allele had improved antinociceptive effect of oxycodone ii. Lesser adverse drug reactions like nausea/vomiting, dizziness, itching and increased adverse drug reactions like urine retention, headaches iii. 3435CC-2677GG was associated with reduced antinociceptive effect of oxycodone	Zwisler et al. (2010)	[47]
		No difference in any of the pain measurements or adverse drug reactions in the first 24 h after surgery	Zwisler et al. (2012)	[48]
		Increased risk of sedation in breastfeeding mothers. No association with oxycodone-induced depression in neonates.	Lam et al. (2012)	[52]
COMT
	Multiple SNPs	22 SNPs within or nearby the COMT gene showed i. 3 SNPs, rs4646312, rs2239393 and rs4818 associated with pain intensity during motion ii. rs887200 (recessive model) and rs1544325 (dominant model) associated with cold pain iii. No association with total oxycodone consumption after multiple testing correction.	Kambur et al. (2013)	[53]
CYP2D6
	PM and EM	i. PM had an increase in pain tolerance thresholds ii. Plasma oxymorphone/oxycodone ratio was lower in PM compared with EM	Zwisler et al. (2009)	[100]
	IM/PM, EM and UM	AUC of oxymorphone were increased while that of noroxycodone were reduced in UM compared with others	Samer et al. (2010)	[36]
	IM/PM, EM and UM	i. CYP2D6 ultra-rapid metabolizers experienced increased pain tolerance thresholds ii. Inverse relation between activity and sedation iii. Psychomotor testing by mean of the digit symbol substitution test should gene dose effect	Samer et al. (2010)	[54]
	PM, EM and UM	i. Significant increase in serum concentrations of oxymorphone and noroxymorphone from PM to EM and from PM to UM ii. No difference between the groups with regard to pain, tiredness and nausea	Andreassen et al. (2012)	[55]
	*4/*4	Trend toward decreased clearance but the effect could not be observed in population pharmacokinetic analysis	Saari et al. (2012)	[46]
	PM, IM and UM	Oxymorphone trough concentrations were higher in EM than in IM but did not affect dose escalation	Naito et al. (2013)	[56]
	PM, IM, EM and UM	Cmax and AUC of oxymorphone and oxymorphone/oxycodone ratio, was increased with EM compared with PM and IM	Balyan et al. (2017)	[57]
	PM, IM, EM and UM	i. *6 and *9 alleles were associated with therapeutic failure in chronic low back pain ii. UM (CYP2D6*2N) associated with an increased risk of side effects	Dagostino et al. (2018)	[58]
CYP3A5
	*3	i. Daily dose escalation rate was increased ii. Noroxycodone trough concentrations were increased with *1	Naito et al. (2013)	[56]

All effects are in relation to the variant allele as notated in the variant column unless otherwise specified.

AUC: Area under curve; EM: Extensive metabolizer; IM: Intermediate metabolizer; PM: Poor metabolizer; UM: Ultra-rapid metabolizer.