Evidence for the efficacy of the emetic PP796 in paraquat SL20 formulations – a narrative review of published and unpublished evidence

Figures & data

Figure 1. A timeline for key meetings, studies and documents.

Table 1. Initial preclinical vomiting studies with PP796.

Species	Number	Dose	Vomited
Dog	8	0.5 mg/kg	3/8 (37.5%)
Dog	8	1.5 mg/kg	6/8 (75.0%)
Pig	8	0.25 mg/kg	0/8 (0%)
Pig	8	0.5 mg/kg	3/8 (37.5%)
Pig	8	1.0 mg/kg	5/8 (62.5%)
Primate	5	0.05 mg/kg	0/5 (0%)
Primate	24	0.1 mg/kg	5/24 (20.8%)
Primate	19	0.2 mg/kg	8/19 (42.1%)
Primate	15	0.3 mg/kg	2/15 (13.3%)
Primate	15	0.4 mg/kg	5/15 (33.3%)
Primate	5	0.5 mg/kg	4/5 (80.0%)
Primate	2	1.0 mg/kg	2/2 (100%)

Table 2. Summary of results from an unpublished pre-clinical dose-response study of PP796 with 20 mg/kg paraquat ion (ref [43,p.296]).

Treatment group	Dog no.	Peak plasma level (mcg/mL)	AUC (0–24 h)	Time to first vomit	Lung lesion (Dark red area)
Paraquat	1	8.9	26.8	1 h 15 min	Moderate
	2	12.5	32.4	29 h	Slight
	3	7.6 ^(1)	48.3 ^(1)	6 h	Marked
Paraquat + 0.5 mg/kg PP796	4	0.7 ^(2)	2.9 ^(2)	24 min	NAD
	5	1.4	4.3	8 min	Minimal
	6	0.8	3.0	26 min	NAD
Paraquat + 3.0 mg/kg PP796	7	0.1	0.5	6 min	NAD
	8	0.6	1.7	5.5 min	NAD
	9	0.4	1.2	4 min	NAD
Paraquat + 20 mg/kg PP796	10	26.7	53.0	1.5 min	Marked
	11	1.4	2.5	3 min	Slight
	12	0.1	0.4	6 min	NAD
	13	0.1	0.5	3 min	Minimal

Notes 1 and 2 indicate that the 8 h results for both these animals were omitted from the analysis. NAD: no abnormalities detected.

Table 3. Time of spontaneous vomiting after ingestion of emetic/non-emetic formulations of paraquat.

	Vomiting		No vomiting
Group	<30 min	>30 min
Non-emetic formulations (n = 21)	4 (19.0%)	4 (19.0%)	13 (61.9%)
Emetic formulations (n = 40)	26 (65.0%)	9 (22.5%)	5 (12.5%)

Adapted from Bramley & Hart, unpublished data.

Reproduced from reference [15].

Robinson M, Brammer A. PP796: emetic study in paraquat treated dogs. CTL/T/2471. Alderley Park (UK): ICI Plc Central Toxicology Laboratory; 1985. [cited 2021 Apr 15]. Available from: https://usrtk.org/wp-content/uploads/2021/03/1995.04.19-ZEN-PQ-EEC-Review-Appendix-A-the-Emetic-PP796-SYNG-PQ-04262278_R-at-2282-2295-1.pdf

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Meredith TJ, Vale JA. Treatment of paraquat poisoning in man: methods to prevent absorption. Hum Toxicol. 1987;6(1):49–55.

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