Hypertension Knowledge Centre
Centrally Acting Drugs
Pharmacokinetics of moxonidine
Pharmacokinetics
About 80-90% of an oral dose of moxonidine is absorbed.76 Bioavailability is 88%, and there is a low degree of protein binding (7%).76 About 10% of the administered dose is metabolised, mainly to 4,5-dehydromoxonidine and a guanidine derivative, both of which have low antihypertensive potency.76
The plasma concentration-time profile of moxonidine after oral administration is shown in figure 28. Peak plasma concentrations of moxonidine in healthy volunteers are reached within 60 minutes after oral administration, and the mean plasma half-life is approximately two hours.76,77
Figure 28: Plasma concentration-time profile of moxonidine after an oral single dose (0.2mg) and after giving 0.2mg bd for 5 days (n=12). Adapted from77
Although there is a relatively short plasma half-life, blood pressure control is satisfactory on a once-daily basis. This is probably because moxonidine is compartmentalised in the brain – i.e., an effective concentration is achieved in the RVLM but this is not reflected in the plasma concentration. Excretion is essentially complete within 24 hours after dosing.76
The pharmacokinetic parameters of moxonidine after single and multiple oral doses of 0.2mg bd are summarised in table 1. Multiple dose studies indicate that moxonidine does not accumulate in plasma with repeated dosing.77,78 The pharmacokinetics of moxonidine are not significantly affected by the ingestion of food.78
Table 1: Mean pharmacokinetic parameters of moxonidine after single and multiple oral doses of 0.2mg bd (n=12). Adapted from 78
| Parameter | Single dose | Multiple dose |
| Time to peak plasma concentration (hr) | 0.74 | 0.67 |
| Peak plasma concentration (ng/ml) | 1.29 | 1.33 |
| Area under the curve (0-infinity) (ng.hr/ml) | 4.18 | 4.02 |
| Terminal half-life (hr) | 2.12 | 1.97 |
| Total clearance (ml/min) | 830 | 863 |
| Renal clearance (ml/min) | 530 | 522 |
Pharmacokinetics in older patients
Moxonidine may be administered without dose adjustment to older patients whose renal function is normal for age. In a parallel-group study, there was no evidence of moxonidine accumulation after five days in older subjects (mean age 71 years, n=12) compared with a younger group (mean age 28 years, n=12).78 Clinically insignificant changes were observed in tmax, AUC and total apparent clearance.
Pharmacokinetics in patients with renal impairment
Elimination half-life and area-under-the-curve are increased in patients with renal impairment, and there is a reduction in the total clearance (figure 29).79 There was no accumulation in patients with moderate renal dysfunction during seven days of treatment. In patients with moderate to severe renal impairment the recommended starting dose is 0.2mg/day; this may be increased to 0.4mg/day if necessary and well tolerated.
Figure 29: Plasma profile of moxonidine (0.3mg once-daily for 7 days) in patients with and without renal impairment (n=8 per group). Adapted from79
Drug interactions
Moxonidine is likely to be used in conjunction with a variety of drugs including cardiac glycosides, other antihypertensives such as diuretics, and oral hypoglycaemic agents. No evidence of substantial pharmacokinetic interaction has been found in studies conducted with representative agents from each of these three groups (e.g., digoxin, hydrochlorothiazide, glibenclamide). Moxonidine has a low degree of protein binding and interaction with highly protein bound drugs such as warfarin would not be anticipated.
The effect of sedatives and hypnotics may be intensified by moxonidine, and the sedative effect of benzodiazepines can be enhanced. Due to lack of therapeutic experience, the use of moxonidine concomitantly with alcohol or tricyclic antidepressants should be avoided. Moxonidine has been co-administered with hypolipidaemic agents (e.g., lovastatin, simvastatin, pravastatin, fenofibrate, gemfibrozil, niacin).
Moxonidine has been administered with other antihypertensive drugs, including thiazide diuretics and calcium-channel blockers. Concomitant administration of these and other antihypertensive agents results in an additive effect.