Safety and Tolerability of Nebulized Amoxicillin-Clavulanic Acid in Patients with COPD (STONAC 1 and STONAC 2)

Figures & data

Table 1. A questionnaire was filled in by the subject after nebulization.

Question	Answer
1. Did you experience adverse effects during or after nebulization?	1 – 2 – 3 – 4 – 5 – 6^*
	^*1 = none, 2 = minor, 3 = moderate, 4 = acceptable, 5 = serious, 6 = severe
2. What adverse events did you experience?	Chest tightness
	Coughing
	Other:…………………………
3. When did these effects occur?	During nebulization / 0 – 10 min /
	10 – 20 min / 20 – 30 min after nebulization
4. Did you need (inhalation) drugs to decrease chest tightness after nebulization?	yes / no

Table 2. Baseline characteristics of enrolled subjects.

STONAC 1
Subject	Gender (m/f)	Age (yrs)	GOLD	FEV1^* (l / %)	VC (l / %)	FEV1/VC (%)
1	M	67	2	1.62 / 53	3.14 / 77	52
2	M	75	2	1.53 / 50	4.99 / 118	31
3	M	69	3	1.55 / 48	3.48 / 81	44
4	M	71	2	1.53 / 50	4.43 / 107	34
5	M	69	2	2.21 / 63	3.96 / 84	56
6	M	75	3	1.44 / 43	3.48 / 75	41
7	M	71	2	2.33 / 74	3.57 / 84	65
8	M	67	3	1.70 / 49	4.24 / 91	40
9	M	78	2	1.59 / 56	3.02 / 77	53
STONAC 2
Subject	Gender (m/f)	Age (yrs)	GOLD	FEV1^* (l / %)	VC (l / %)	FEV1/VC (%)
1	M	72	3	1.51 / 47	2.60 / 59	58
2	F	73	1	1.52 / 84	2.27 / 104	67
3	M	67	4	0.58 / 22	2.05 / 57	28
4	F	82	2	1.65 / 78	2.86 / 112	58
5	F	65	3	1.01 / 42	2.29 / 80	44
6	F	58	2	2.13 / 84	3.51 / 118	61
7	F	63	3	1.19 / 55	1.99 / 78	60
8	F	54	2	1.94 / 70	3.22 / 99	60

^*STONAC 1 at start of first nebulization.

^*STONAC 2 stable phase.

Figure 1. (A) the change in FEV₁ before-after nebulization in stable COPD patients. (STONAC 1). Change in FEV₁ was measured at each nebulization. No clinical relevant reduction of FEV₁ (> 20%) occurs after nebulizations of amoxicillin clavulanic acid. (B) the change in FEV₁ before-after nebulization in COPD exacerbation patients. (STONAC 2). Change in FEV₁ was measured once for each subject. No clinical relevant reduction of FEV₁ (> 20%) occurs after nebulizations of amoxicillin clavulanic acid.

Figure 2. STONAC 1 Amoxicillin concentration in sputum samples collected within 3 hours after nebulization.

Table 3. STONAC 2: Amoxicillin concentration in sputum samples collected before the second nebulization (trough samples)

Patient no.	Concentration amoxicillin (mg/l)
1	–
2	–
3	9.77
4	1.65
5	138
6	500
7	26
8

Subjects 1, 2, and 8 were not able to produce sputum at that moment.