Table 3.

Pharmacokinetics and Pharmacodynamics of OTC Cough and Cold Drug Components in Pediatrics

Drugs	Pharmacokinetics Process	Pharmacokinetic Parameters		Pharmacodynamics	References
Acetaminophen	Absorption	Bioavailability	~72%	The analgesic effects are thought to be brought on by the activation of descending serotonergic inhibitory pathways in the CNS, while the antipyretic effects result from the inhibition of the hypothalamus heat-regulating center	[51–54]
		pKa	9.38
	Distribution	Volume distribution	0.85–1.5 L/kg
		Protein binding	10–30%
	Metabolism	-	Metabolized in the liver to sulfate and glucuronide conjugates.
	Excretion	T ½	2.6–2.8 hours
		Clearance	400 mL/minute
Pseudoephedrine	Absorption	Bioavailability	N/A	It directly stimulates beta-adrenergic receptors, while indirectly it activates alpha-adrenergic receptors, triggering the release of endogenous norepinephrine from neuronal granules	[55–57]
		pKa	10.25
	Distribution	Volume distribution	~2.5 L/kg
		Protein binding	20%
	Metabolism		Metabolized in the liver to produce active nor-pseudoephedrine (<1%).
	Excretion	T ½	~3 hours
		Clearance	7.3–7.6 mL/minute/kg
Dextromethorphan	Absorption	Bioavailability	11%	It works by reducing the sensitivity of cough receptors and preventing the transmission of cough impulses by suppressing the medullary cough center through the activation of sigma receptors	[51,58–60]
		pKa	9.8
	Distribution	Volume distribution	5.0–6.7 L/kg
		Protein binding	60–70%
	Metabolism	-	Metabolized in the liver to dextrorphan (active) and lower quantities of 3-hydroxy and 3-methoxy derivatives.
	Excretion	T ½	4.9–6.41 hours
		Clearance	33.8 mL/minute/ kg
CTM	Absorption	Bioavailability	59%	It is competing with histamine for H1-receptor sites on effector cells in the respiratory system, gastrointestinal tract, and blood vessels	[61–64]
		pKa	9.2
	Distribution	Volume distribution	7 L/kg
		Protein binding	29–37%
	Metabolism		Metabolized in the liver to active and inactive metabolites.
	Excretion	T ½	13.1 hours
		Clearance	N/A

Abbreviations: CTM, chlor-trimeton or chlorpheniramine maleate; pKa is the acid dissociation constant; T½, half-life of a drug; CNS, central nervous system; N/A, not available.